Vaccines doi: 10.3390/vaccines13010008

Authors: Wannes Philips Andy Haegeman Nina Krešić Laurent Mostin Nick De Regge

Background: Vaccination is the main control measure to prevent Lumpy skin disease (LSD), and Neethling-based homologous vaccines have been shown to be safe and effective against infection with classical clade 1.2 strains. In 2017, recombinant clade 2 LSDV strains originating from a badly produced and insufficiently controlled vaccine were first detected in Russia. A clade 2.5 recombinant strain spread from Russia throughout Southeast Asia and caused a massive epidemic. In this study, the efficacy of three different Neethling strain-based vaccines against the recombinant clade 2.5 LSDV strain was evaluated. Methods: For each vaccine, seven bulls were vaccinated and followed for three weeks to evaluate vaccine safety. Thereafter, vaccinated animals and non-vaccinated controls were challenged with a virulent clade 2.5 strain and followed for three more weeks to evaluate vaccine efficacy. Results: Only limited adverse effects were observed after vaccination, and all vaccinated animals seroconverted and showed an LSDV-specific cellular immune response after vaccination. After the challenge, the vaccinated animals developed almost no clinical signs, and no viremia or nasal excretion was detected. This was in sharp contrast with the non-vaccinated controls, where 8 out of 13 animals developed clinical disease with clear nodules. Most of these animals also had a prolonged period of fever, a clear viremia and excreted virus. Conclusions: Neethling-based LSDV vaccines can thus be considered safe and are effective not only against clade 1.2 LSDV strains, as was proven earlier, but also against a clade 2.5 recombinant strain.

Vaccines doi: 10.3390/vaccines13010007

Authors: Nadezhda Wall Rachel Lamerton Fiona Ashford Marisol Perez-Toledo Aleksandra Jasiulewicz Gemma D. Banham Maddy L. Newby Sian E. Faustini Alex G. Richter Haresh Selvaskandan Roseanne E. Billany Sherna F. Adenwalla Ian R. Henderson Max Crispin Matthew Graham-Brown Lorraine Harper Adam F. Cunningham

Background/Objectives: Generalised immune dysfunction in chronic kidney disease, especially in patients requiring haemodialysis (HD), significantly enhances the risk of severe infections. Vaccine-induced immunity is typically reduced in HD populations. The SARS-CoV-2 pandemic provided an opportunity to examine the magnitude and functionality of antibody responses in HD patients to a previously unencountered antigen—Spike (S)-glycoprotein—after vaccination with different vaccine platforms (viral vector (VV); mRNA (mRV)). Methods: We compared the total and functional anti-S antibody responses (cross-variant neutralisation and complement binding) in 187 HD patients and 43 healthy controls 21–28 days after serial immunisation. Results: After 2 doses of the same vaccine, HD patients had anti-S antibody levels and a complement binding capacity comparable to controls. However, 2 doses of mRV induced greater polyfunctional antibody responses than VV (defined by the presence of both complement binding and cross-variant neutralisation activity). Interestingly, an mRV boost after 2 doses of VV significantly enhanced antibody functionality in HD patients without a prior history of SARS-CoV-2 infection. Conclusions: HD patients can generate near-normal, functional antigen-specific antibody responses following serial vaccination to a novel antigen. Encouragingly, exploiting immunological memory by using mRNA vaccines and boosting may improve the success of vaccination strategies in this vulnerable patient population.

Vaccines doi: 10.3390/vaccines13010006

Authors: Ines Aguinaga-Ontoso Sara Guillen-Aguinaga Laura Guillen-Aguinaga Rosa Alas-Brun Miriam Guillen-Aguinaga Luc Onambele Enrique Aguinaga-Ontoso Esperanza Rayón-Valpuesta Francisco Guillen-Grima

Background: The COVID-19 pandemic disrupted routine child immunization efforts, threatening to reverse progress in controlling vaccine-preventable diseases. Materials and Methods: We analyzed the impact of COVID-19 on DTP3 vaccination in Europe by comparing trends before and after the pandemic using time series data from 2000 to 2023. Employing joinpoint regression, chi-square tests, and segmented regression analysis, we assessed DTP3 vaccination trends and coverage changes. Results: The findings revealed significant regional disparities across Europe. Statistical models indicated reductions in DTP3 coverage in countries such as Ireland, Sweden, and Switzerland, whereas Ukraine and San Marino showed improvements. Conclusions: There are variations in the effect of COVID-19 on DTP3 coverage rates, indicating the need for targeted public health strategies to address vaccine hesitancy, logistical barriers, and systemic inequities.

Vaccines doi: 10.3390/vaccines13010005

Authors: Jingshan Huang Hongxia Wu Tianqi Gao Huanjie Zhai Assad Moon Xin Song Shuwen Li Zhanhao Lu Jing Lan Dailang Zhong Xinyu Zhang Hua-Ji Qiu Yongfeng Li Yuan Sun

Background/Objectives: African swine fever (ASF), caused by African swine fever virus (ASFV), poses a significant threat to the global swine industry. This underscores the urgent need for safe and effective ASF vaccines. Methods: Here, we constructed five bacterium-like particles (BLPs) that each display one of the five ASFV antigens (F317L, H171R, D117L, B602L, and p54) based on the Gram-positive enhancer matrix-protein anchor (GEM-PA) system. GEM is a bacterial particle that contains only peptidoglycan, while PA is composed of three lysin motifs (Lysm) derived from the C-terminus of the AcmA protein, capable of non-covalently binding to GEM. By fusing the ASFV antigens with PA, the ASFV antigens can be firmly attached to the surface of GEM. Subsequently, the piglets were immunized via intramuscular injection with a mixture of BLPs-F317L, BLPs-H171R, BLPs-D117L, BLPs-B602L, and BLPs-p54. Results: The results showed that the piglets developed detectable serum IgG antibodies 2 weeks after the first immunization, and these high antibody levels were maintained 4 weeks after the booster immunization. Moreover, these piglets produced more IFN-γ-producing lymphocytes than the control piglets. Conclusions: The data indicate that the generated BLPs mixture can stimulate both humoral and cellular immune responses in piglets, these five ASFV proteins are promising antigens, and the BLPs generated represent candidate ASF vaccines.

Vaccines doi: 10.3390/vaccines13010004

Authors: Liyan Zhu Ying Han Jiahai Lu Jianhao Tan Conghui Liao Cheng Guo Qing He Yajie Qiu Huahua Lu Yue Zhou Jianrui Wei Dandan Hu

Background: The influenza virus’s high mutation rate requires the annual reformulation and administration of the vaccine. Therefore, its vaccine effectiveness (VE) must be evaluated annually. Aim: Estimate the effectiveness of the influenza vaccine and analyze the impact of age, seasonal variations, and the vaccination to sample collection interval on VE. Methods: The study used a test-negative case–control (TNCC) design to collect data from patients under 18 years of age who presented with acute respiratory infection (ARI) symptoms and underwent influenza virus testing at a national children’s regional medical center in Guangdong Province between October 2021 and January 2024, spanning three influenza seasons. VE was estimated using unconditional logistic regression. Results: A total of 27,670 patient data entries were analyzed. The VE against all influenza viruses across the three seasons was 37% (95% CI: 31–43), with the lowest VE of 24% (95% CI: 8–37) observed in the 2021–2022 season. In children aged 0.5 to <3 years, the VE was 32% (95% CI: 19–43). The effectiveness for samples collected at intervals of 0.5–2 months, 3–6 months, and over 6 months after vaccination was 39% (95% CI: 32–46), 30% (95% CI: 19–40), and 28% (95% CI: 5–46). Conclusions: Across three influenza seasons, at least one-third of vaccinated individuals were protected from influenza in outpatient settings. Given that children are at high risk, improving vaccination management is recommended, and parents should be encouraged to vaccinate their children before each influenza season.

Vaccines doi: 10.3390/vaccines13010003

Authors: Luisa Müller Venkata A. S. Dabbiru Lucy Rutten Rinke Bos Roland Zahn Stefan Handtke Thomas Thiele Marta Palicio Olga Esteban Marta Broto Tom Paul Gordon Andreas Greinacher Jing Jing Wang Linda Schönborn

Background/Objectives: Adenoviral vector-based vaccines against COVID-19 rarely cause vaccine-induced immune thrombocytopenia and thrombosis (VITT), a severe adverse reaction caused by IgG antibodies against platelet factor 4 (PF4). To study VITT, patient samples are crucial but have become a scarce resource. Recombinant antibodies (rAbs) derived from VITT patient characteristic amino acid sequences of anti-PF4 IgG are an alternative to study VITT pathophysiology. Methods: Amino acid sequences of the variable region of immunoglobulin light and heavy chain of anti-PF4 IgG derived from VITT patients were obtained by mass spectrometry sequencing and rAbs were synthetized by reverse-engineering. Six different rAbs were produced: CR23003, CR23004, and CR23005 (from a patient vaccinated with Jcovden, Johnson & Johnson-Janssen (Beerse, Belgium)), CR22046, and CR22050 and CR22066 (from two different patients vaccinated with Vaxzevria, AstraZeneca (Cambridge, UK)). These rAbs were further characterized using anti-PF4 and anti-PF4/heparin IgG ELISAs, rapid anti-PF4 and anti-PF4/polyanion chemiluminescence assays, and PF4-induced platelet activation assay (PIPA) and their capacity to induce procoagulant platelets. Results: rAbs bound to PF4 alone, but not to PF4/polyanion complexes in rapid chemiluminescence assays. Chemiluminescence assays and both anti-PF4 IgG and anti-PF4 IgG/heparin ELISA showed concentration-dependent PF4 binding of all six rAbs, however, with different reactivities among them. PIPA showed a similar, concentration-dependent platelet activation pattern. rAbs varied in their reactivity and the majority of the tested rAbs were able to induce procoagulant platelets. Conclusions: The six rAbs derived from VITT patients reflect VITT-typical binding capacities and the ability to activate platelets. Therefore, these rAbs offer an attractive new option to study VITT pathophysiology.

Vaccines doi: 10.3390/vaccines13010002

Authors: Jaturawitt Prasopsiri Kanjana Srisutthisamphan Benjamas Liwnaree Juggragarn Jengarn Jarin Kramyu Payuda Hansoongnern Papon Muangsanit Nathiphat Tanwattana Challika Kaewborisuth Suttipun Sungsuwan Anan Jongkaewwattana Nanchaya Wanasen

Background: Middle East Respiratory Syndrome Coronavirus (MERS-CoV) causes severe respiratory illness in humans and currently lacks an approved vaccine. The Newcastle disease virus (NDV) vector is a well-established, safe, and effective platform for vaccine development. With recent advancements in stabilizing coronavirus spike proteins to enhance their antigenicity, this study aimed to determine whether modifications to the MERS-CoV spike protein could improve its presentation on NDV particles, allowing the resulting virus to be used as an inactivated vaccine. Methods: We codon-optimized the gene encoding the ectodomain of the MERS-CoV spike protein and incorporated modifications at the S1/S2 and S2’ cleavage sites, along with a proline substitution at residues V1060-L1061. This modified spike gene was inserted into the NDV genome to create the NDV-SMERS virus. After purification and inactivation, the vaccine’s immunogenicity was assessed in mice. Results: Mice immunized with the inactivated NDV-SMERS vaccine developed robust anti-spike IgGs, neutralizing antibodies, and cellular immune responses. The study demonstrated that modifications to the MERS-CoV spike protein were essential for its effective presentation on NDV particles. Additionally, the spike gene insert remained stable through five egg passages, confirming the vector’s stability. Conclusions: Engineering the MERS-CoV spike protein is crucial for its successful display on NDV particles. The strong immune responses elicited by the NDV-SMERS vaccine in mice highlight that NDV is a promising, safe, and effective platform for MERS-CoV vaccination.

Vaccines doi: 10.3390/vaccines13010001

Authors: Shixu Song Jialing Gan Qiuyue Long Zhancheng Gao Yali Zheng

The persistent threat of COVID-19, particularly with the emergence of new variants, underscores the urgency for innovative therapeutic strategies beyond conventional antiviral treatments. Current immunotherapies, including IL-6/IL-6R monoclonal antibodies and JAK inhibitors, exhibit suboptimal efficacy, necessitating alternative approaches. Our review delves into the significance of NAD+ metabolism in COVID-19 pathology, marked by decreased NAD+ levels and upregulated NAD+-consuming enzymes such as CD38 and poly (ADP-ribose) polymerases (PARPs). Recognizing NAD+’s pivotal role in energy metabolism and immune modulation, we propose modulating NAD+ homeostasis could bolster the host’s defensive capabilities against the virus. The article reviews the scientific rationale behind targeting NAD+ pathways for therapeutic benefit, utilizing strategies such as NAD+ precursor supplementation and enzyme inhibition to modulate immune function. While preliminary data are encouraging, the challenge lies in optimizing these interventions for clinical use. Future research should aim to unravel the intricate roles of key metabolites and enzymes in NAD+ metabolism and to elucidate their specific mechanisms of action. This will be essential for developing targeted NAD+ therapies, potentially transforming the management of COVID-19 and setting a precedent for addressing other infectious diseases.

Vaccines doi: 10.3390/vaccines12121450

Authors: Michaela Cain Qinfeng Huang Shania Sanchez Hinh Ly Yuying Liang

Background: Live viral vector-based vaccines are known to elicit strong immune responses, but their use can be limited by anti-vector immunity. Here, we analyzed the immunological responses of a live-attenuated recombinant Pichinde virus (PICV) vector platform (rP18tri). Methods: To evaluate anti-PICV immunity in the development of vaccine antigen-specific immune responses, we generated a rP18tri-based vaccine expressing the lymphocytic choriomeningitis virus (LCMV) nucleoprotein (NP) and administered four doses of this rP18tri-NPLCMV vaccine to mice. Using MHC-I tetramers to detect PICV NP38-45 and LCMV NP396-404 epitope-specific CD8+ T cells, we monitored vector- and vaccine-antigen-specific immune responses after each vaccination dose. Results: LCMV NP396-404-specific effector and memory CD8+ T cells were detected after the first dose and peaked after the second dose, whereas PICV NP38-45-specific memory CD8+ T cells increased with each dose. PICV-binding IgG antibodies peaked after the second dose, while anti-PICV neutralizing antibodies (NAbs) remained low even after the fourth dose. Immunization with the rP18tri-NPLCMV vaccine significantly reduced LCMV viral titers in a chronic LCMV Clone 13 infection model, demonstrating the protective role of LCMV NP-specific T cells. Conclusion: These findings provide important insights into the antigen- and vector-specific immunity of the rP18tri-NPLCMV vaccine and support the development of NP-based vaccines against arenavirus pathogens.

Vaccines doi: 10.3390/vaccines12121452

Authors: Noemí López-Perea Teresa López-Cuadrado Aurora Fernández-García Juan E. Echevarría Josefa Masa-Calles

Background/Objectives: Spain has been in a measles elimination phase since 2014. No evidence exists about the distribution of measles cases among the population born outside Spain. The aim of this study was thus to describe the epidemiological situation of measles, stratified by place of birth, during the post-elimination period in Spain. Methods: This is a retrospective study of confirmed measles cases reported to RENAVE between 2014 and 2022. A descriptive analysis of case characteristics (sex, age group, vaccination status, imported case) was performed, was well as an analysis of temporal trends and geographic distribution in measles incidence rate (IR; cases/million inhabitants). All analyses were stratified by place of origin (Spain born vs. born outside Spain). We then performed a sensitivity analysis of those born outside Spain, with the representation of Kaplan–Meier curves taking into account the year of arrival in the country until the onset of measles. Results: Between 2014 and 2022, 951 measles cases were reported in Spain (overall IR: 2.3). Among these, 18.6% (177 cases, IR: 3.0) were born outside Spain. The IRs show differences (p < 0.001) in terms of distribution by age group and origin. By age group, children under 5 years had the highest IR, but adults aged 30 years and older reported the highest proportion of cases. The incidence rate ratio (IRR) was 5-fold higher among foreign-born children under 5 years than among native-born children. The measles time trend shows the highest peak in 2019 for foreign-born and native-born (IR: 8.6 and 5.4, respectively), consistent with the European-wide scenario, while only one case of measles was reported in 2022. Geographical variability in incidence rates by region was observed: Catalonia and the Valencian Community accumulated the highest proportion of cases throughout the study period. Among those born outside Spain, the median time from arrival to onset of rash was 6 years. Conclusions: The incidence of measles is 40% higher in Spain’s foreign-born population than in its native-born population. Taking into account the increasing migrant population in Spain, we consider that public health efforts need to be directed towards susceptible groups of people. In this context of advanced elimination, specific interventions for identifying and attending the most vulnerable populations should be designed and implemented.

Vaccines doi: 10.3390/vaccines12121451

Authors: Irene Segato Dalila Mele Greta Forlani Daniela Dalla Gasperina Mario U. Mondelli Stefania Varchetta

Background/Objectives: New SARS-CoV-2 variants are continuously emerging, making it essential to assess the efficacy of vaccine-induced immune protection. Limited information is available regarding T cell responses to BA.2.86 and JN.1 variants, particularly in elderly individuals. Methods: We evaluated T cell and total IgG responses against the receptor-binding domain (RBD) of the ancestral SARS-CoV-2 strain, as well as BA.2.86 and JN.1 omicron subvariants, in two groups of subjects. One group consisted of SARS-CoV-2-exposed elderly individuals who were fully vaccinated with the BNT162B2 mRNA vaccine, with a booster dose of the updated 2023–2024 COVID-19 vaccine (XBB.1.5) at least 15 days after receiving a booster dose of the updated 2023–2024 COVID-19 vaccine. The second group consisted of healthcare workers who were unexposed to SARS-CoV-2 one month after the booster dose of the first-generation BNT162b2 mRNA vaccine. T cell activation-induced markers (AIM) and IFN-γ secretion were evaluated by flow cytometry and ELISpot assays, respectively. Results: Elderly subjects showed reduced IgG levels against JN.1 compared with the ancestral strain. BA.2.86 stimulation resulted in lower IFN-γ levels in the elderly versus the COVID-19-naïve group. AIM analysis showed that among T cells, CD4+ were the most responsive, with a reduced proportion of JN.1-reactive CD4+ T cells compared with the ancestral strain in the SARS-CoV-2-unexposed group. Despite receiving the updated booster, the elderly group showed reduced CD4+ T cell reactivity to BA.2.86. Conclusions: The XBB.1.5-containing vaccine induced lower CD4+ T cell responses against BA.2.86 in the elderly. CD4+ T cells from BNT16b2-vaccinated, COVID-19-naïve subjects recognized ancestral and BA.2.86 RBD strains while showing reduced responses to JN.1. These results emphasize the need for tailored vaccine strategies for emerging variants, particularly in vulnerable populations.

Vaccines doi: 10.3390/vaccines12121448

Authors: Yanjuan He Jiaxin Wang Lanyan Chi Yajing Dong Huixin Chen Xiaocui Meng Ming Liao Yongwen Luo Huiying Fan

Background: Recombinant avian influenza subunit vaccines often require adjuvants to enhance immune responses. This study aims to evaluate the immune-enhancing potential of seven combination adjuvants in specific pathogen-free (SPF) chickens. Methods: SPF chickens were vaccinated with combinations of ISA78VG and adjuvants, including Quil-A, CpG, and monophosphoryl lipid A (MPLA). Their immune responses were assessed using a vaccination and viral challenge protection model. Results: The combinations of ISA78VG with Quil-A, CpG&MPLA or CpG&Quil-A significantly enhanced antibody responses and provided cross-protection against the H5N8-20135 strain. The ISA78VG&MPLA and ISA78VG&CpG&MPLA combinations induced the stronger IFN-γ production, with CpG further amplifying the immune response. The ISA78VG&Quil-A formulation, in particular, stimulated rapid antibody responses, achieving a 100% seroconversion by day 14 and high titers of hemagglutination inhibition (HI) antibodies against both the recombinant HA antigen and the H5N6-20053 virus. Conclusions: The ISA78VG&Quil-A combination is an ideal adjuvant for enhancing the immunogenicity of avian influenza rHA subunit vaccines, offering a promising strategy for H5 subtype vaccine development.

Vaccines doi: 10.3390/vaccines12121449

Authors: André Silva-Pinto Isabel Abreu António Martins Juliana Bastos Joana Araújo Ricardo Pinto

Background/Objectives: Haematopoietic stem cell transplantation (HCT) induces profound immunosuppression, significantly increasing susceptibility to severe infections. This review examines vaccinations’ necessity, timing, and efficacy post-HCT to reduce infection-related morbidity and mortality. It aims to provide a structured protocol aligned with international and national recommendations. Methods: A systematic review of current guidelines and studies was conducted to assess vaccination strategies in HCT recipients. The analysis included the timing of vaccine administration, factors influencing efficacy, and contraindications. Recommendations for pre- and post-transplant vaccination schedules were synthesised, specifically for graft-versus-host disease (GVHD), immunosuppressive therapy, and hypogammaglobulinemia. Results: Vaccination is essential as specific immunity is often lost after HCT. Inactivated vaccines are recommended to commence three months post-transplant, including influenza, COVID-19, and pneumococcal vaccines. Live attenuated vaccines remain contraindicated for at least two years post-transplant and in patients with ongoing GVHD or immunosuppressive therapy. Factors such as GVHD and immunosuppressive treatments significantly impact vaccine timing and efficacy. The review also underscores the importance of pre-transplant vaccinations and ensuring that patients’ close contacts are adequately immunised to reduce transmission risks. Conclusions: Implementing a structured vaccination protocol post-HCT is critical to improving patient outcomes. Timely and effective vaccination strategies can mitigate infection risks while addressing individual patient factors such as GVHD and immunosuppression. This review highlights the need for tailored vaccination approaches to optimize immune reconstitution in HCT recipients.

Vaccines doi: 10.3390/vaccines12121447

Authors: Omayma Abdalla Nada Ahmed Hanan Abdo El-Hag Mukhtar Susan Reef Jose Hagan Gavin Grant

Background/Objectives: Congenital rubella syndrome (CRS) is a constellation of serious multi-organ birth defects following rubella virus infection during early pregnancy. Countries in which rubella vaccination has not yet been introduced can have a high burden of this disease. Data on CRS burden and epidemiology are needed to guide the introduction of a rubella vaccine and monitor progress for rubella elimination, but the multi-system nature of CRS manifestations and required specialized testing creates a challenge for conducting CRS surveillance in developing settings such as Sudan. To enhance data quality, we designed and tested a simplified approach for CRS surveillance in Sudan. Methods: Seven CRS surveillance sentinel sites were set up at general pediatric, eye, and cardiology hospitals in Sudan, using standard definitions for reporting and classifying infants with CRS clinical manifestations. Between 2014 and 2017, we evaluated the system using WHO CRS surveillance monitoring indicators, comparing simplified approaches against a comprehensive one. The simplified approaches included (1) an ophthalmic-focused approach; (2) a heart-focused approach; and (3) a cataract-only approach. Results: Surveillance identified 179 infants with suspected CRS via the comprehensive approach, with 25 infants classified as laboratory-confirmed and 6 as clinically compatible. Surveillance sensitivity was highest for the simplified ophthalmic approach, while cataract-based surveillance had the highest proportion of confirmed cases. Conclusions: Simplified CRS surveillance, particularly focusing on detecting cataracts, can significantly contribute to monitoring the impact of rubella vaccine introduction. It could serve as an initial step towards comprehensive CRS surveillance, providing robust evidence to support rubella and CRS elimination efforts.

Vaccines doi: 10.3390/vaccines12121446

Authors: William Martin Catarina Luís Stefan Jungbluth Monika Slezak Frank A. W. Verreck Holger Spiegel Carlos A. Guzman António Roldão Manuel J. T. Carrondo Peter Van der Ley Joaquim Segalés Hazel M. Dockrell Mei Mei Ho Gabriel K. Pedersen Maria Lawrenz Ole F. Olesen

TRANSVAC represents a long-running effort to accelerate the development of novel vaccines by integrating institutions from across Europe under a single collaborative framework. This initiative has empowered the global vaccine community since 2009 including contributing toward the development and optimization of vaccine candidates as well as the provision of new adjuvants, research protocols, and technologies. Scientific services were provided in support of 88 different vaccine development projects, and 400 professionals attended TRANSVAC training events on various vaccine-related topics. Here, we review the accomplishments of the TRANSVAC consortia and analyze the continued needs of academic and industrial vaccine developers in Europe. The findings highlight the benefits of coordination across different sectors, both through research infrastructures such as TRANSVAC and other mechanisms, to address the current and future global health challenges and ensure that European vaccine developers have the support required to successfully compete in the global market.

Vaccines doi: 10.3390/vaccines12121445

Authors: Christopher J. Hernandez Kavya G. Sundar Fernando Echegaray Mary Catherine Cambou Lanbo Z. Yang Eddy R. Segura Marineide Gonçalves de Melo Breno Riegel Santos Ivana Rosângela dos Santos Varella Karin Nielsen-Saines

Objectives: SARS-CoV-2 infection is a known risk factor for adverse health outcomes in pregnancy, affecting both maternal and neonatal health. Mounting evidence suggests that even a single dose of an approved COVID-19 vaccine protects against severe SARS-CoV-2 infection and is safe for both pregnant persons and neonates. Southern Brazil was heavily affected by the COVID-19 pandemic, and the protective effects of the vaccine on maternal and neonatal health are not well described. This study aims to examine the protective effects of maternal COVID-19 vaccination on both maternal and neonatal outcomes following SARS-CoV-2 infection during pregnancy. Methods: This is a retrospective cohort study that leveraged medical data from a tertiary center in South Brazil to compare maternal and infant outcomes between hospitalized pregnant persons with and without SARS-CoV-2 infection between 1 March 2020, and 1 March 2023. Results: In total, 524 patients were enrolled, including 275 pregnant patients with confirmed SARS-CoV-2 infection and 249 without infection. SARS-CoV-2 infection was associated with maternal ventilator support (adjusted Risk Ratio [aRR] = 1.48, 95% Confidence Interval [95% CI]: 1.08–2.03), while receipt of at least one dose of COVID-19 vaccine was associated with protection against maternal sepsis (aRR = 0.14, 95% CI: 0.03–0.56), intensive care unit (ICU) admission (aRR = 0.27, 95% CI: 0.10–0.68), need for ventilator support (aRR = 0.60, 95% CI: 0.43–0.84), infant admission to the neonatal intensive care unit (NICU) (aRR = 0.62, 95% CI: 0.47–0.82), and neonatal respiratory distress (aRR = 0.60, 95% CI: 0.43–0.83). Conclusions: These findings further underscore the importance of maternal vaccination against COVID-19 during pregnancy. Even one dose of vaccine was protective against a variety of maternal and neonatal outcomes. Prenatal care should encourage COVID-19 vaccination in pregnancy.

Vaccines doi: 10.3390/vaccines12121444

Authors: Achilleas Livieratos Lars Erik Schiro Charalambos Gogos Karolina Akinosoglou

Background/Objectives. Research on respiratory virus immunity duration post-vaccination reveals variable outcomes. This study performed a literature review to assess the efficacy and longevity of immune protection post-vaccination against SARS-CoV-2, influenza, and respiratory syncytial virus (RSV), with a focus on immunocompromised populations. Specific objectives included examining humoral and cellular immune responses and exploring the impact of booster doses and hybrid immunity on extending protection. Methods. A literature review was conducted focusing on studies published from January 2014 to November 2024. The search targeted adaptive immunity post-vaccination, natural immunity, and hybrid immunity for SARS-CoV-2, influenza, and RSV. Selection criteria emphasized human populations, adaptive immunity outcomes, and immunocompromised individuals. The PICO framework guided the analysis, culminating in a detailed review of 30 studies. Results. SARS-CoV-2 vaccines exhibited robust initial antibody responses, which waned significantly within six months, necessitating frequent boosters. Influenza and RSV vaccines similarly showed declines in immunity, though some influenza vaccines demonstrated moderate durability. Hybrid immunity, arising from combined natural infection and vaccination, provided more resilient and lasting protection than vaccination alone, especially against emerging variants. Immunocompromised individuals consistently exhibited reduced durability in adaptive immune responses across all studied viruses. Challenges include rapid viral mutations, limiting the broad protection of current vaccines. Conclusions. Immune durability varies significantly across virus types and patient populations. Frequent boosters and hybrid immunity are critical to optimizing protection, particularly for vulnerable groups. The findings underscore the need for adaptable vaccination strategies and advancements in vaccine design to counter rapidly mutating respiratory pathogens effectively.

Vaccines doi: 10.3390/vaccines12121443

Authors: Andrey Koltsov Mikhail Sukher Sergey Krutko Sergey Belov Alexey Korotin Sofia Rudakova Sergey Morgunov Galina Koltsova

Background/Objectives: The spread of African swine fever virus (ASFV) has led to major economic losses to pork worldwide. In Russia, there are no developed or registered vaccines against ASFV genotype II, which is associated with numerous ASFV outbreaks in populations of domestic pigs and wild boars in the country. Methods: We introduced deletions of the six MGF360 and MGF505 genes of the ASFV virulent Stavropol_01/08 strain, isolated in Russia in 2008. Results: We show here that this deletion did lead to full attenuation of the ASFV virulent Stavropol_01/08 strain. Animals intramuscularly inoculated with 104 HAD50 of ΔMGF360/505_Stav developed a strong immune response and short period of viremia (at 3–7 days post-inoculation). Recombinant ΔMGF360/505_Stav strain provides complete protection of pigs against the ASFV parental Stavropol_01/08 strain (103 HAD50). Therefore, in our experiment, we did not detect the genome of both the virulent and the recombinant strains in the blood and organs post-challenge with the Stavropol_01/08. In contrast, we found only partial protection (40%) of the ΔMGF360/505_Stav-immunized pigs against challenge with the ASFV heterologous Rhodesia strain. Additionally, the surviving animals had a prolonged fever, and their condition was depressed for most of the experiment. Conclusions: Thus, the ASFV recombinant ΔMGF360/505_Stav strain is the first live attenuated vaccine (LAV) in Russia that induces complete protection in pigs challenged with the highly virulent, epidemiologically relevant strains genotype II and serotype 8. However, this ASF LAV is not able to provide a high level of protection against other variants of serotype 8.

Vaccines doi: 10.3390/vaccines12121442

Authors: Kimberly C. McKeirnan Megan R. Undeberg Skylar Zelenko Ghazal Meratnia

Background/Objectives: Rural communities in the United States experience increased disparity of care for both general healthcare services and access to routine vaccines. Previous research has indicated a 40% lower vaccination rate in rural communities, as compared to urban counterparts. Having a better understanding regarding factors influencing lower vaccination rates in rural areas could help public health officials prepare for future vaccination efforts. This research sought to gather and evaluate the opinions of people who live and work in rural areas regarding barriers to COVID-19 vaccine uptake. Methods: A semi-structured qualitative key informant interview design was utilized by researchers to gather opinions from university Extension staff in Washington State. Interview transcripts were analyzed using the Theory of Planned Behavior (ToPB) framework to evaluate COVID-19 vaccination-related intentions and motivational factors that the Extension staff observed among rural populations in their communities. Results: Twenty-one participants representing 34 out of the 40 Extension offices responded and were interviewed during fall 2023. Using the ToPB constructs, nine barriers were identified. Attitude-related barriers included the following: inherent social distancing in rural location negating vaccine necessity; lack of early vaccine availability in rural locales; concerns regarding ineffectiveness of the vaccine; and inadequate dissemination of vaccine information to non-English language speakers and those with limited access to technology. Subjective norm barriers included the following: perception of exclusion of rural populations’ unique needs during design and implementation of vaccine mandates; exertion of social pressures on rural individuals’ vaccine uptake decision; and highly visible breakdown in standard trust in core community institutions and leadership. Barriers related to loss of perceived behavioral control included vaccine mandates impacting self-perceived loss of autonomy and limitations in vaccine technology information impacting perception of vaccine safety. Conclusions: By identifying barriers to vaccination in rural communities during the COVID-19 pandemic, future outreach efforts can be designed to improve intention and lead to stronger vaccination uptake.

Vaccines doi: 10.3390/vaccines12121441

Authors: María Yolanda Cervantes-Apolinar Adriana Guzman-Holst Abiel Mascareñas De los Santos Alejandro Ernesto Macías Hernández Álvaro Cabrera Argelia Lara-Solares Carlos Abud Mendoza Daniel Motola Kuba Diana Fabiola Flores Díaz Fernanda Salgado Gomez Graciela Elia Castro-Narro Javier Nieto José Antonio Mata-Marín José Fernando Barba Gómez Juan Carlos Tinoco Juan Manuel Calleja Castillo Maria Margarita Contreras Serratos Nathali Castellanos Ramos Oscar Rosas Carrasco Raúl Ricaño Gloria C. Huerta García

Herpes zoster (HZ) is a common disease in older adults and immunocompromised patients, and is frequently associated with long-term complications that impact quality of life. Fortunately, more than one vaccine against HZ is now available in Mexico. Two expert consensus groups discussed adult vaccination strategies in Mexico, focusing on HZ in older adults and immunocompromised individuals; their insights are reported here. HZ is usually treated inappropriately in Mexico. Late diagnosis and suboptimal management are common, as is a lack of treatment options, particularly for pain, which is often unresponsive to standard painkillers. Improving vaccination rates against HZ in Mexico is therefore important, but several barriers to HZ vaccination exist. It is not included in the national vaccination schedule, where included vaccines usually have higher coverage. Actions to overcome barriers include improving awareness of HZ and vaccine availability, developing and promoting guidelines and recommendations for vaccination, and expanding access and infrastructure for vaccination.

Vaccines doi: 10.3390/vaccines12121440

Authors: Yuejie Zhu Yueyue He Ziyue Yin Na Chen Xingxing Qi Jianbing Ding Yujiao Li Fengbo Zhang

Background: Echinococcosis is a zoonotic infectious disease that poses a significant threat to the health of individuals living in rural regions. While vaccination represents a potential strategy for disease prevention, there is currently no effective vaccine available for humans to prevent cystic echinococcosis (CE). This study aimed to design a novel multi-epitope vaccine (MEV) against Echinococcus granulosus for human use, employing immunoinformatics methods. Methods: We identified core epitopes from two key antigens, EgA31 and EgG1Y162, and integrated them into the immunoglobulin variable region of CTLA-4 (CTLA-4lgV) to create the CVE31-162 vaccine construct. The secondary and tertiary structures of the CVE31-162 were established using bioinformatics methods. The interaction between the CVE31-162 and B7 molecules was assessed through molecular dynamics simulations. Finally, both in vitro and in vivo experiments were conducted to validate the effectiveness of the CVE31-162 against the immunological effects of Echinococcus granulosus. Results: Bioinformatics analysis indicated that CVE31-162 exhibits favorable antigenicity, stability, and non-allergenicity. Furthermore, CVE31-162 demonstrated a stable three-dimensional structural model. Molecular docking (MD) and molecular dynamics simulations (MDS) revealed a strong binding affinity between CVE31-162 and B7 molecules. Immune simulation results suggested that the vaccine elicits robust humoral and cell-mediated immune responses. Both in vitro and in vivo experiments demonstrated that immunized mice exhibited significantly elevated levels of antigen-specific antibodies and enhanced lymphocyte proliferation compared to the control group. Conclusions: CVE31-162, which is based on the interaction between CTLA-4 and B7, represents a promising multi-epitope vaccine for Echinococcus granulosus.

Vaccines doi: 10.3390/vaccines12121439

Authors: Thomas Meyer Eggert Stockfleth

HPV-associated dermatological diseases include benign lesions like cutaneous warts and external genital warts. In addition, HPV infection is associated with the development of epithelial skin cancers, in particular cutaneous squamous cell carcinoma (cSCC). In contrast to anogenital and oropharyngeal cancers caused by mucosal HPV types of genus alpha papillomavirus, cSCC-associated HPV types belong to the genus beta papillomavirus. Currently available HPV vaccines that target mucosal HPV types associated with anogenital cancer and genital warts are type-specific and provide no cross-protection against beta HPV. When implementing vaccination to beta HPV to prevent skin tumors, it must be considered that acquisition of these HPV types occurs early in childhood and that the risk for cSCC increases with growing age and decreasing immune surveillance. Thus, individuals considered for beta HPV vaccination usually have pre-existing infection and are largely immunocompromised. On the other hand, worldwide increasing incidence rates of epithelial skin cancer reflect an urgent need for skin cancer prevention measures. Based on the pathogenic involvement of beta HPV, vaccination may represent a promising prevention strategy. Indeed, various procedures of prophylactic and therapeutic vaccination have been developed, and some of them have shown efficiency in animal models. Thus far, however, none of these vaccine candidates has been approved for application in humans.

Vaccines doi: 10.3390/vaccines12121438

Authors: Andrea Ceccarelli Gabriele Munafò Francesco Sintoni Christian Cintori Davide Gori Marco Montalti

Background: General practitioners (GPs) and primary care units collaborate with Prevention Departments (PDs) to improve immunization by participating in vaccination campaigns, sharing tools, and implementing educational programs to raise patient awareness. This review aimed to identify effective strategies for involving GPs in PD vaccination practices. Methods: A systematic review following PRISMA guidelines was conducted on MEDLINE, TripDatabase, ClinicalTrials, CINAHL, and Cochrane up to January 2024 to identify full-text studies in English evaluating the effectiveness of GP involvement. A meta-analysis was also performed. Results: Of 1018 records, 15 studies were included, with an intermediate quality assessment. Studies originated from the United States (n = 9), Europe (5), Singapore (1), and China (1). Eight studies investigated educational programs for GPs, while seven focused on organizational or technological interventions to enhance immunization practices. Twelve studies reported increased vaccine uptake after intervention. Vaccines addressed included influenza, SARS-CoV-2, pneumococcal, zoster, and trivalent (diphtheria, tetanus, pertussis). Interventions involving GPs in PD vaccination campaigns, focusing on organizational or technological strategies, demonstrated a significant increase in vaccine uptake (OR = 1.15; 95% CI: 1.03–1.27; p < 0.0001; I2 = 96%). Conclusions: GPs emerged as valuable allies for PDs due to their extensive territorial reach and trusted relationships with patients. Additionally, up-to-date organizational and technological tools could play a decisive role in increasing vaccine uptakes. This study, offering valuable insights into the effectiveness of GPs involvement, may be useful to implement similar intervention in different contexts.

Vaccines doi: 10.3390/vaccines12121437

Authors: Adaku Anyiam-Osigwe Thando Katangwe-Chigamba Sion Scott Carys Seeley Amrish Patel Erika J. Sims Richard Holland Veronica Bion Allan B. Clark Alys Wyn Griffiths Liz Jones Adam P. Wagner David J. Wright Linda Birt

Background/Objectives: Vaccinating care home staff is essential to protect vulnerable residents by reducing infection risks and creating a safer care environment. However, vaccine hesitancy amongst staff remains a challenge, particularly since the COVID-19 pandemic raised concerns about side effects and vaccination mandates. This study examines how the pandemic influenced flu vaccine hesitancy amongst UK care home staff. Methods: Data were collected from the FluCare trials conducted over the 2021–22 and 2022–23 winter seasons to explore the impact of concurrent mandatory and non-mandatory COVID-19 vaccination policies on flu vaccine uptake. A total of 52 interviews (21 from the feasibility study and 31 from the randomised control trial) were conducted with care home managers and staff. Thematic analysis identified key themes shaping staff attitudes toward flu vaccination. Results: Four central themes emerged regarding the impact of the pandemic on staff attitudes and the contextual influences shaping vaccine hesitance: (i) tension between autonomy and morals in vaccination decisions; (ii) the COVID ‘craze’ and the displacement of the flu vaccine; (iii) the role of the COVID ‘craze’ in staff vaccine fatigue; and (iv) conspiracies, (mis)information, and the significance of trust. Psychosocial theories on decision making and health behaviour were used to further interpret the findings. Conclusions: Our findings suggest that post-COVID-19 interventions in care home setting should address the issues of autonomy, vaccine fatigue, and trust to enhance vaccine uptake. Understanding these factors could support more effective strategies to address hesitancy amongst care home staff in future vaccination campaigns.

Vaccines doi: 10.3390/vaccines12121436

Authors: Xiaojing Li Su Jin Shuyang Guo Dan Yang Wenbo Sai Xiao Qiu Xin Zhao Lan Wang Tao Wang Min Li

The concept of “platform technology” gained prominence after the Ebola outbreak and since then has become essential to international vaccine (prophylactic vaccines against infectious disease) regulatory frameworks. Its significance was further amplified during the COVID-19 pandemic, where platform technology enabled the rapid development and approval of vaccines, optimizing regulatory processes, and enhancing global public health responses. As a transformative tool, platform technology streamlines product development, allowing for the reduction in the number of clinical trials or exemption from certain clinical trials and facilitating cross-referencing in regulatory submissions. Despite significant efforts to establish standardized regulatory procedures, challenges remain, particularly in achieving a unified definition and application of platform technology across regions. This paper explores the evolution, applications, and regulatory strategies of platform technology, with a focus on China’s experience in this field. China’s approach, encompassing risk assessment, and the expedited approval of emergency vaccines, offers valuable insights into global regulatory coordination. By analyzing China’s regulatory contributions and international practices, this paper highlights the potential of platform technology to address future pandemics, including “Pathogen X”, and underscores the importance of harmonizing global regulatory efforts to strengthen public health preparedness and response.

Vaccines doi: 10.3390/vaccines12121435

Authors: Maarten Swart Jessica Allen Brendan Reed Ana Izquierdo Gil Johan Verspuij Sonja Schmit-Tillemans Anish Chakkumkal Mark Findeis Angela V. Hafner Chandresh Harjivan Rebecca Kurnat Harmjan Kuipers Roland Zahn Boerries Brandenburg

Human metapneumovirus (HMPV) is a significant respiratory pathogen, particularly in vulnerable populations. Background: No vaccine for the prevention of HMPV is currently licensed, although several subunit vaccines are in development. Saponin-based adjuvant systems (AS), including QS-21, have transformed the field of subunit vaccines by dramatically increasing their potency and efficacy, leading to the development of several licensed vaccines. However, naturally sourced tree bark-extracted QS-21 faces supply and manufacturing challenges, hindering vaccine development. Objective: This study reports on an alternative plant cell culture system for the consistent production of highly pure QS-21. Method: We evaluated the efficacy of cultured plant cell (cpc)-produced QS-21 in a novel HMPV vaccine, formulating a recombinant pre-fusion stabilized HMPV F protein (preF) with cpcQS-21 and a synthetic toll-like receptor 4 (TLR4) agonist adjuvant formulation. Results: In mice, TLR4 agonist containing adjuvant formulations with plant cell-produced QS-21 performed equally to licensed adjuvant AS01 containing tree-bark-extracted QS-21 and demonstrated a significant increase in immunogenicity against HMPV preF compared to the unadjuvanted control. Conclusion: Our findings pave the way for a reliable, scalable, and sustainable source of pure QS-21, enabling the development of highly effective HMPV and other vaccines with significant public health impact.

Vaccines doi: 10.3390/vaccines12121434

Authors: Yan Mathias Alves Thaís Zamboni Berra Reginaldo Bazon Vaz Tavares Nathalia Zini Quézia Rosa Ferreira Licia Kellen de Almeida Andrade Ariela Fehr Tártaro Maria Eduarda Pagano Pelodan Beatriz Fornaziero Vigato Beatriz Kuroda Silveira Ana Luiza Brasileiro Nato Marques Assumpção Marcela Antunes Paschoal Popolin Patricia Abrahão Curvo Simone Protti-Zanatta Maria Del Pilar Serrano-Gallardo Ricardo Alexandre Arcêncio Pedro Fredemir Palha Jaqueline Garcia de Almeida Ballestero

Introduction: Vaccines are a significant public health achievement, which are crucial for child survival and disease control globally. In Brazil, the National Immunization Program (PNI) manages vaccination schedules, including essential vaccines like BCG and Hepatitis B, administered at birth. Despite achieving over 95% coverage for years, vaccination rates have declined since 2016, a trend exacerbated by the COVID-19 pandemic. This study aims to analyze spatial and temporal trends in BCG and Hepatitis B vaccination coverage at birth, identify areas with spatial variation in these trends, classify the identified trends, and investigate the pandemic’s impact on vaccination adherence. Methods: This is an ecological study with real-world data from Brazil, focusing on vaccination coverage from 2014 to 2023. Utilizing the Spatial Variation in Temporal Trends (SVTT) technique, the study identifies municipalities’ vaccination trends. It also employs time series analysis and Interrupted Time Series methods to evaluate the pandemic’s impact on vaccination rates, using data from the PNI and the Information System on Live Births (SINASC). Results: Between January 2014 and December 2023, Brazil administered 25,902,207 doses of the BCG vaccine to children at birth, with 3911 municipalities (70.24%) showing declining trends, particularly in Florianópolis. Similarly, 22,962,434 doses of the Hepatitis B vaccine were administered, with 3284 municipalities also experiencing declines. Conclusions: It is crucial that public health policies be reevaluated to address regional disparities in vaccination coverage, particularly in more vulnerable areas. Focused interventions, such as awareness campaigns, improved access to vaccination services, and strengthened monitoring, are fundamental to reversing this trend.

Vaccines doi: 10.3390/vaccines12121433

Authors: Gyneth Lourdes G. Bibera Peter San Martin Desiree A. M. van Oorschot Afif Nurul Hidayati Deliana Permatasari Sasheela Sri La Sri Ponnampalavanar Kughan Govinden Maria Christina Filomena Batac Joselito Javier Terapong Tantawichien Phatu Boonmahittisut Trinh Minh Trang Thanh Tuyen Dang Thi

The burden of herpes zoster (HZ) is recognized worldwide; however, there is seemingly limited information on incidence and vaccination practices in Southeast Asia (SEA). A scientific workshop was held by the Zoster Experts’ Network to exchange and consolidate insights on the burden of HZ and the patient pathway in SEA. The workshop included practicing clinical experts and public health specialists/epidemiologists from Indonesia, Malaysia, the Philippines, Thailand, and Vietnam. It aimed to identify gaps in the literature, outline patient pathways, and evaluate HZ vaccine recommendations among these countries. Consensus was identified on the substantial lack of epidemiological data on HZ in SEA and the need to investigate the impact of age, immunocompromising conditions, and comorbidities on the incidence and severity of HZ in the region. However, available data in SEA did indicate a rising disease and socioeconomic burden of HZ, with concerns that current treatment strategies for HZ are suboptimal. The HZ patient pathways generated by the experts highlighted common themes and differences between the five countries. Furthermore, the experts highlighted the lack of awareness of HZ and its impact on patients’ quality of life, among patients and healthcare professionals. Evaluation of the current local HZ vaccine recommendations further showed differences in age and the inclusion of at-risk populations between countries. The workshop outcomes emphasize the need for further HZ surveillance in SEA. Efforts to align and address leakage within the patient pathway and raise awareness on the impact of HZ should be prioritized. Awareness initiatives and alignment on vaccine recommendations are also needed.

Vaccines doi: 10.3390/vaccines12121432

Authors: Haley Echlin Amy Iverson Abigail McKnight Jason W. Rosch

Background: Acute otitis media (AOM) is a common pediatric infection worldwide and is the primary basis for pediatric primary care visits and antibiotic prescriptions in children. Current licensed vaccines have been incompletely ineffective at reducing the global burden of AOM, underscoring a major unmet medical need. The complex etiology of AOM presents additional challenges for vaccine development, as it can stem from multiple bacterial species including Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. As such, targeting multiple pathogens simultaneously may be required to significantly impact the overall disease burden. Methods: In this study, we aim to overcome this challenge by engineering a live-attenuated vaccine platform based on an attenuated mutant of S. pneumoniae that expresses H. influenzae and M. catarrhalis surface epitopes to induce protective immunity against all three pathogens. Results: The trivalent live-attenuated vaccine conferred significant protection against all three bacterial otopathogens as measured by seroconversion and the development of AOM, with the inclusion of the additional epitopes providing unexpected synergy and enhanced protection against S. pneumoniae. Conclusions: These data demonstrate a novel mechanism of introducing non-native immunogenic antigens into a live-attenuated vaccine platform to engender protection against AOM from multiple pathogenic species.

Vaccines doi: 10.3390/vaccines12121431

Authors: Ann Levin Teemar Fisseha Heidi W. Reynolds Gustavo Corrêa Tewodaj Mengistu Nancy Vollmer

Introduction: A limited number of studies focus on estimating the costs of interventions to increase childhood immunization coverage in low- and middle-income countries (LMICs). Existing reviews often compare estimated costs but lack information on the methods used. The objective of this review is to summarize the methods used in costing studies that assessed interventions to reach zero-dose (ZD) children. Methods: We conducted a review of existing studies that estimate the costs of increasing childhood vaccination and reducing prevalence of ZD children in LMICs. We conducted searches of PubMed using terms including “immunization”, “cost”, “coverage increase”, “zero-dose”, and “LMIC”, and further extended our search to bibliographies and gray literature from organizations working to reach ZD children. We only included articles that estimated the cost of interventions to increase childhood vaccination and/or reach ZD children and not articles about introducing new vaccines or other age groups. We categorized each article according to their costing methods, cost components, types of costs calculated, and presence of uncertainty analysis. Results: Eleven articles met our inclusion criteria. Interventions costs varied from USD 0.08 per additional dose for SMS reminders in Kenya to USD 67 per dose for cash transfers in Nicaragua. Most of the studies were from South Asia: India (4), Pakistan (2), and Bangladesh (1). The rest were from Africa (3) and Latin America (1). Most articles did not include a description of their costing methods. Only three described their methods in detail. Conclusions: Few studies have estimated the costs of increasing childhood vaccination coverage and reducing the number of ZD children in LMICs. The wide variation in intervention costs underscores the need for standardized costing methodologies to enhance comparability across studies. Only three studies detailed their costing methods, making comparisons challenging. Establishing research principles for costing ZD interventions could strengthen future evidence for policymaking.

Vaccines doi: 10.3390/vaccines12121430

Authors: Yauba Saidu Jessica Gu Budzi Michael Ngenge Sangwe Clovis Nchinjoh Amani Adidja Nnang Edwidge Nkwain Muteh Clarence Mbanga Diaby Ousmane Andreas Njoh Junie Flegere Demba Diack Emanuele Montomoli Sue Ann Costa Clemens

Background/Objectives: A “people-centered” approach is one of the core principles of the Immunization Agenda (IA) 2030 and emphasizes the need for services to be organized around the needs and expectations of individuals and the community. A better understanding of the immunization experience from the client’s perspective is key to guiding the design of policies and interventions aimed at improving immunization delivery and coverage. This study provides a synthesis of the immunization experiences of children’s caregivers in Cameroon, highlighting potential barriers for timely and complete immunization. Methods: A descriptive cross-sectional study was conducted, targeting caregivers of children brought to selected health facilities for immunization in all ten regions of Cameroon. Using structured questionnaires, data were collected from caregivers and analyzed using STATA version 13. Results: In total, 1230 caregivers were interviewed in 265 health facilities. The median age of participants was 27 years and the median number of children per caregiver was two children. Most (87%) of the study participants reported to be satisfied with immunization service delivery. The median waiting time for vaccination was 1 h 48 min, with regional median waiting times ranging from 18 min in the South region to 4 h 6 min in the North region. About a quarter (24%) of surveyed participants reported to have presented to a health facility for immunization services and were turned away without achieving the purpose for which they came at least once. About half (48%) of the caregivers had never heard about planned vaccination activities in their communities. Conclusion: While most caregivers appeared to be satisfied with immunization service delivery in Cameroon, our study highlights some notable caregiver concerns (long waiting times, unproductive immunization visits and inadequate information about outreach activities) which, if addressed, may go a long way to enhance the immunization experience of caregivers in Cameroon, build trust in immunization services and thus improve vaccination uptake.

Vaccines doi: 10.3390/vaccines12121429

Authors: Jessica R. Watts Jennifer L. Spencer Clinton Jeroen Pollet Rongsheng Peng Jie Tan Paul D. Ling

Background/Objectives: Elephant endotheliotropic herpesvirus (EEHV) causes lethal hemorrhagic disease (HD) in Asian and African elephants in human care and the wild. It is the leading cause of death for young Asian elephants in North American and European zoos despite sensitive diagnostic tests and improved treatments. Thus, there is a critical need to develop an effective vaccine to prevent severe illness and reduce mortality from EEHV-HD. We generated a multi-antigenic EEHV mRNA vaccine to address this need that encodes the EEHV1A-subtype glycoproteins gB, gH, gL, and gO. These conserved proteins are the entry machinery for several herpesviruses in the betaherpesvirus subfamily and elicit humoral and cellular immunity in naturally infected elephants. Methods: Outbred CD-1 mice were vaccinated with two doses of an mRNA vaccine comprising modified EEHV1A gB, gH, gL, and gO mRNAs encapsulated into lipid nanoparticles. Humoral and T-cell immunity was assessed three weeks after the first dose or three weeks after the booster dose using luciferase immunoprecipitation system assays and flow cytometry, respectively. Results: The CD-1 mice vaccinated once had detectable antibody titers against gB, gH, and gL that increased significantly three weeks after a booster dose. Activated CD4+ and CD8+ T cells secreting cytokines associated with a TH1 response were induced against all four glycoproteins. No adverse effects were observed following one or two doses of the vaccine. Conclusions: We found that gB, gH, gL, and gO as a multivalent vaccine stimulated robust humoral and cell-mediated immunity. This is a critical step for moving this candidate EEHV1A mRNA vaccine into clinical trials in Asian elephants.

Vaccines doi: 10.3390/vaccines12121428

Authors: Samara Sousa de Pinho Maria da Conceição Viana Invenção Anna Jéssica Duarte Silva Larissa Silva de Macêdo Benigno Cristofer Flores Espinoza Lígia Rosa Sales Leal Marco Antonio Turiah Machado da Gama Ingrid Andrêssa de Moura Micaela Evellin dos Santos Silva Débora Vitória Santos de Souza Marina Linhares Lara Julia Nayane Soares Azevedo Alves Antonio Carlos de Freitas

Background/Objectives: DNA vaccines are rapidly produced and adaptable to different pathogens, but they face considerable challenges regarding stability and delivery to the cellular target. Thus, effective delivery methods are essential for the success of these vaccines. Here, we evaluated the efficacy of capsules derived from the cell wall of the yeast Pichia pastoris as a delivery system for DNA vaccines. Methods: The capsules were extracted from the yeast Pichia pastoris strain GS115, previously grown in a YPD medium. pVAX1 expression vector was adopted to evaluate the DNA vaccine insertion and delivery. Three encapsulation protocols were tested to identify the most effective in internalizing the plasmid. The presence of plasmids inside the capsules was confirmed by fluorescence microscopy, and the encapsulation efficiency was calculated by the difference between the initial concentration of DNA used for insertion and the concentration of unencapsulated DNA contained in the supernatant. The capsules were subjected to different temperatures to evaluate their thermostability and were co-cultured with macrophages for phagocytosis analysis. HEK-293T cells were adopted to assess the cytotoxicity levels by MTT assay. Results: The microscopy results indicated that the macrophages successfully phagocytosed the capsules. Among the protocols tested for encapsulation, the one with 2% polyethylenimine for internalization showed the highest efficiency, with an encapsulation rate above 80%. However, the vaccine capsules obtained with the protocol that used 5% NaCl showed better thermal stability and encapsulation efficiency above 63% without induction of cell viability loss in HEK 293T. Conclusions: We successfully described a vaccine delivery system using yeast capsules derived from Pichia pastoris, demonstrating its potential for DNA vaccine delivery for the first time. Additional studies will be needed to characterize and improve this delivery strategy.

Vaccines doi: 10.3390/vaccines12121427

Authors: Tom C. Quach Mitchell G. Miglis Lu Tian Hector Bonilla Phillip C. Yang Lauren Grossman Amogha Paleru Vincent Xin Anushri Tiwari Robert W. Shafer Linda N. Geng

Introduction: COVID-19 vaccinations reduce the severity and number of symptoms for acute SARS-CoV-2 infections and may reduce the risk of developing Long COVID, also known as post-acute sequelae of SARS-CoV-2 (PASC). Limited and heterogenous data exist on how these vaccinations received after COVID-19 infection might impact the symptoms and trajectory of PASC, once persistent symptoms have developed. Methods: We investigated the association of post-COVID-19 vaccination with any SARS-CoV-2 vaccine(s) on PASC symptoms in two independent cohorts: a retrospective chart review of self-reported data from patients (n = 128) with PASC seen in the Stanford PASC Clinic between May 2021 and May 2022 and a 2023 multinational survey assessment of individuals with PASC (n = 484). Findings: Within the PASC Clinic patient cohort (n = 128), 58.6% (n = 75) were female, and 41.4% (n = 53) were male; 50% (n = 64) were white, and 38.3% (n = 49) were non-white. A total of 60.2% (n = 77) of PASC Clinic patients reported no change in their PASC symptoms after vaccination, 17.2% (n = 22) reported improved symptoms, and 22.7% (n = 29) reported worsened symptoms. In the multinational survey cohort (n = 484), 380 were from the U.S., and 104 were from outside the U.S.; 88.4% (n = 428) were female, and 11.6% (n = 56) were male; and 88.8% (n = 430) were white, and 11.2% (n = 54) were non-white. The distribution of survey self-reported vaccine effects on PASC symptoms was 20.2% worsened (n = 98), 60.5% no effect (n = 293), and 19.2% improved (n = 93). In both cohorts, demographic features, including age, sex, and race/ethnicity, were not significantly associated with post-vaccination PASC symptom changes. There was also a non-significant difference in the median dates of COVID-19 infection among the different outcomes. BMI was significant for symptom improvement (p = 0.026) in the PASC Clinic cohort, while a history of booster doses was significant for symptom improvement (p < 0.001) in the survey cohort. Conclusions: Most individuals with PASC did not report significant changes in their overall PASC symptoms following COVID-19 vaccinations received after PASC onset. Further research is needed to better understand the relationship between COVID-19 vaccinations and PASC.

Vaccines doi: 10.3390/vaccines12121426

Authors: Filipe Abadesso Lopes Miguel Miranda André Ye Joana Rodrigues Paulo Pé-Leve José Palma Reis Ricardo Pereira e Silva

Background/Objectives: Urinary tract infections (UTI) represent a highly frequent and debilitating disease. Immunoactive prophylaxis, such as the polyvalent bacterial whole-cell-based sublingual vaccine MV140, have been developed to avoid antibiotic use. However, the effectiveness of this tool in the Portuguese population is still unknown. This study aims at assessing the effectiveness of treatment with MV140 in a cohort of Portuguese patients presenting with recurrent UTIs. Methods: Prospective observational real-life study of 125 patients with complicated and uncomplicated recurrent UTIs treated with MV140. The primary outcome was a reduction in frequency and severity of UTIs after a follow-up of 12 months. Overall satisfaction, adverse events, and assessment of the effectiveness of MV140 in subgroups of patients with specific risk factors for UTIs were secondary outcomes. Results: In the 12 months after treatment outset, 38% of patients were UTI-free, 34% reported 1 or 2 UTI episodes, and the remaining 28% presented 3 or more UTIs, corresponding to a mean reduction of 3.20 (2.87–3.53, 95% C.I.; p < 0.001) UTI episodes per year per patient. The effectiveness of MV140 was the same regardless of sex, BMI, regular sexual activity, hypertension, diabetes mellitus, depression, paraplegia, performance of intermittent self-catheterization, indwelling bladder catheter, or previous use of other UTI-preventing vaccines. We observed a higher effectiveness in post-menopausal women compared to pre-menopausal (74.7% vs. 59.4%, respectively, p = 0.029). A total of 73% of patients reported a reduction in symptom severity or days of disease, and the mean global satisfaction was 7.52/10. Conclusions: MV140 demonstrated to be effective in the reduction rate of recurrent UTIs in a cohort of adult Portuguese patients.

Vaccines doi: 10.3390/vaccines12121425

Authors: Imran Mirza

During the COVID-19 pandemic, over 13 [...]

Vaccines doi: 10.3390/vaccines12121424

Authors: Gertrude Noufack Placide Bissengue Junior Koma Zobanga Junior Stève Cyrille Malingao Mory Keita Marie Constance Razaiarimanga Marie-Eve Raguenaud

Background/Objectives: Yellow fever (YF) outbreaks continue to affect populations that are not reached by routine immunization services, such as workers at a high risk of occupational exposure to YF. In the Central African Republic (CAR), YF cases were detected in districts characterized by the presence of workers in forest areas. We developed an innovative approach based on a local partnership with private companies of the extractive industry to administer YF vaccine to workers in remote areas during the response to an outbreak. Methods: The planning stage of the campaign included the mapping of forestry and mining companies through the involvement of national and/or local representatives of companies from both the formal and informal sectors. Information sessions and mobilization targeted the heads of operating companies. Advanced and mobile strategies were used to target workers on their work site. Companies provided logistical support including transportation and communication and set up temporary vaccination posts. Results: Using this local partnership, it was possible to vaccinate over 70,000 workers (5.8% of the entire vaccinated population) in hard-to-reach areas, protecting them from YF. This represented around 47% of the estimated number of workers and dependents. The partnership with the private sector also contributed to increasing knowledge on the risk of YF and means of protection among a high-risk community. Conclusions: Private companies represent potentially useful actors that can contribute to the protection of high-risk workers and to the prevention and control YF outbreaks. The experience in the CAR has demonstrated that it is possible to obtain support from private companies, including informal ones, for a vaccination campaign.

Vaccines doi: 10.3390/vaccines12121423

Authors: Haiyan Zhang Arun Sridhar Natacha Delrez Bo He Sophie Fourny Yuan Gao Owen Donohoe Alain F. C. Vanderplasschen

Background/Objectives: Anguillid herpesvirus 1 (AngHV-1) (recently renamed Cyvirus anguillidallo 1) is the etiologic agent of a lethal disease that affects several eel species. It is thought to be one of the main infectious agents causing a population decline in wild eels and economic loss within the eel aquaculture sector. To date, no vaccines are available against AngHV-1. Recently, we developed a safe and efficacious live attenuated recombinant vaccine against Cyprinid herpesvirus 3 (CyHV-3). This CyHV-3 recombinant vaccine encodes a deletion of ORF57. Orthologues of CyHV-3 ORF57 exist in Cyprinid herpesvirus 2 (CyHV-2, ORF57) and AngHV-1 (ORF35). Methods: In the present study, using recombinant strains and bioluminescent in vivo imaging, we investigated the effect of AngHV-1 ORF35 deletion on virus replication in vitro, virulence in vivo, and the potential of an AngHV-1 ORF35-deleted recombinant as a vaccine candidate for the mass vaccination of eels by immersion. With this goal in mind, we produced ORF35-deleted recombinants using two parental strains: a UK strain and a recombinant derived from the former strain by insertion of a Luciferase–GFP reporter cassette into a non-coding intergenic region. Results: Analyses of ORF35-deleted recombinants led to the following observations: (i) AngHV-1 ORF35 is not essential for viral growth in cell culture, and its deletion does not affect the production of extracellular virions despite reducing the size of viral plaque. (ii) In contrast to what has been observed for CyHV-3 ORF57 and CyHV-2 ORF57, in vivo bioluminescent analyses revealed that AngHV-1 ORF35 is an essential virulence factor and that its deletion led to abortive infection in vivo. (iii) Inoculation of the AngHV-1 ORF35-deleted recombinant by immersion induced a protective immune response against a wild-type challenge. This protection was shown to be dose-dependent and to rely on the infectivity of AngHV-1 ORF35-deleted virions. Conclusions: This study suggests that the AngHV-1 ORF35 protein has singular properties compared to its orthologues encoded by CyHV-2 and CyHV-3. It also supports the potential of AngHV-1 ORF35-deleted recombinants for the mass vaccination of eels by immersion.

Vaccines doi: 10.3390/vaccines12121422

Authors: Mónika Madai Dániel Hanna Roland Hetényi Fanni Földes Zsófia Lanszki Brigitta Zana Balázs Somogyi Henrietta Papp Anett Kuczmog Orsolya Faragó-Sipos Csaba Nemes Vilmos Palya Dávid Géza Horváth Gyula Balka Krisztián Bányai Xinkai Jia Péter Balogh Pál Bajnóczi

Background/Objectives: The ongoing COVID-19 pandemic has underscored the need for alternative prophylactic measures, particularly for populations for whom vaccines may not be effective or accessible. This study aims to evaluate the efficacy of intranasally administered IgY antibodies derived from hen egg yolks as a protective agent against SARS-CoV-2 infection in Syrian golden hamsters, a well-established animal model for COVID-19. Methods: Hens were immunized with the spike protein of SARS-CoV-2 to generate IgY antibodies. These antibodies were extracted from the egg yolks, purified, and their neutralizing activity was tested in vitro. Syrian golden hamsters were then treated with the IgY antibodies before being challenged with SARS-CoV-2. Viral loads were quantified using droplet digital PCR (ddPCR), and lung pathology was assessed through histopathological analysis. Results: The in vitro assays showed that IgY effectively neutralized SARS-CoV-2. In the in vivo hamster model, IgY treatment led to a significant reduction in viral loads and a marked decrease in lung consolidation and inflammation compared to the positive control group. Histopathological findings further supported the protective role of IgY in reducing lung damage caused by SARS-CoV-2. Conclusions: The results demonstrate that IgY antibodies exhibit strong antiviral activity and can significantly reduce SARS-CoV-2 viral loads and associated lung pathology in hamsters. These findings suggest that IgY could be a viable prophylactic option for preventing SARS-CoV-2 infection, particularly for individuals who cannot receive or respond to vaccines. Further studies are warranted to optimize dosage and explore the long-term efficacy of IgY antibodies.

Vaccines doi: 10.3390/vaccines12121421

Authors: Sandra Kannampuzha Anirban Goutam Mukherjee Uddesh Ramesh Wanjari Abilash Valsala Gopalakrishnan Reshma Murali Arunraj Namachivayam Kaviyarasi Renu Abhijit Dey Balachandar Vellingiri Harishkumar Madhyastha Raja Ganesan

Following the publication of paper [...]

Vaccines doi: 10.3390/vaccines12121420

Authors: Muzaffar Muminov Nargiza Tsiferova Egor Pshenichnov Khusnora Ermatova Oksana Charishnikova Alisher Abdullaev Yuliya Levitskaya Dilbar Dalimova Sandhya MVS Geetanjali Tomar Ankush Dewle Pradhnya Choudhari Aditi Wangikar Amol Jadhav Mrunal Mule Pralhad Wangikar Ibrokhim Abdurakhmonov Shahlo Turdikulova

Background: The development of effective and safe vaccines and their timely delivery to the public play a crucial role in preventing and managing infectious diseases. Many vaccines have been produced and distributed globally to prevent COVID-19 infection. However, establishing effective vaccine development platforms and evaluating their safety and immunogenicity remains critical to increasing health security, especially in developing countries. Objectives: Therefore, we developed a local subunit vaccine candidate, RENOVAC, and reported its toxicity and immunogenicity profile in animal models. Methods: First, the synthetic gene-coding tandem RBD linked with the GS linker was cloned into the expression vector and expressed in CHO cells. The protein was then purified and filter sterilized, and 10 µg/dose and 25 µg/dose formulations were finally examined for the 14-day repeated dose toxicity followed by the immunogenic profile in preclinical studies. Results: When administered to Sprague Dawley rats by intramuscular route, the vaccine was well tolerated up to and including the dose of 25 µg/animal, and no toxicologically adverse changes were noted. The observed change in weight of the thymus and spleen might be related to the immunological response to the vaccine. The dimer RBD vaccine demonstrated the ability to generate high levels of specific immunoglobulins (IGs) and neutralization antibodies (NAbs). Finally, changes in the amounts of specific T cells and cytokines after vaccination suggested that the vaccine mainly triggers an immune response by activating CD4+ Th2-cells, which then activate B-cells to provide humoral immunity. Conclusions: The study suggests that, based on its reliable immunogenicity and acceptable safety, the vaccine can be further directed for clinical trials.

Vaccines doi: 10.3390/vaccines12121419

Authors: Vilija Gurkšnienė Tadas Alčauskas Fausta Majauskaitė Ligita Jančorienė

Background and Objectives: Given that COVID-19 vaccination is a relatively recent development, particularly when compared to immunisation against other diseases, it is crucial to assess its efficacy in vaccinated populations. This literature review analysed studies that monitored antibody titres against SARS-CoV-2 in healthcare workers who received COVID-19 vaccines. Methods: Using the PICO (Population, Intervention, Comparators, Outcomes) model recommended in the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines we included 43 publications which analyse antibody dynamics following primary vaccination, the effects of booster doses, and the influence of factors such as COVID-19C infection, age, and sex on antibody kinetics. Results: All the studies demonstrated a strong immunogenic response to the vaccines. Re-gardless of the vaccine used, over 95% of the pre-vaccination seronegative population be-came seropositive in all studies. Depending on the sampling intervals provided by the re-searchers, antibody levels were quantitatively highest during the first three months after vaccination, but levels inevitably declined over time. The monthly decline in antibodies observed in all these studies highlighted the necessity for booster doses. Studies analysing the impact of revaccination on antibody dynamics have confirmed that revaccination is an effective tool to boost humoral immunity against SARS-CoV-2. An-tibodies appear to persist for a longer period of time after revaccination, although they are subject to similar factors influencing antibody dynamics, such as age, comorbidities, and exposure to COVID-19. In addition, heterogeneous revaccination strategies have been shown to be more effective than homogeneous revaccination. Conclusions: Our review demonstrated that antibody levels against SARS-CoV-2 inevitably decline after vaccination, leaving the question of ongoing booster strategies open. The studies reviewed provided evidence of the effectiveness of booster vaccination, despite differences in age, sex, and prior COVID-19 infection. This suggests that repeated vaccination remains a highly effective method for mitigating the continued threat posed by COVID-19.

Vaccines doi: 10.3390/vaccines12121418

Authors: Rossella Brandi Alessia Paganelli Raffaele D’Amelio Paolo Giuliani Florigio Lista Simonetta Salemi Roberto Paganelli

mRNA vaccines represent a milestone in the history of vaccinology, because they are safe, very effective, quick and cost-effective to produce, easy to adapt should the antigen vary, and able to induce humoral and cellular immunity. Methods: To date, only two COVID-19 mRNA and one RSV vaccines have been approved. However, several mRNA vaccines are currently under development for the prevention of human viral (influenza, human immunodeficiency virus [HIV], Epstein–Barr virus, cytomegalovirus, Zika, respiratory syncytial virus, metapneumovirus/parainfluenza 3, Chikungunya, Nipah, rabies, varicella zoster virus, and herpes simplex virus 1 and 2), bacterial (tuberculosis), and parasitic (malaria) diseases. Results: RNA viruses, such as severe acute respiratory syndrome coronavirus (SARS-CoV)-2, HIV, and influenza, are characterized by high variability, thus creating the need to rapidly adapt the vaccines to the circulating viral strain, a task that mRNA vaccines can easily accomplish; however, the speed of variability may be higher than the time needed for a vaccine to be adapted. mRNA vaccines, using lipid nanoparticles as the delivery system, may act as adjuvants, thus powerfully stimulating innate as well as adaptive immunity, both humoral, which is rapidly waning, and cell-mediated, which is highly persistent. Safety profiles were satisfactory, considering that only a slight increase in prognostically favorable anaphylactic reactions in young females and myopericarditis in young males has been observed. Conclusions: The COVID-19 pandemic determined a shift in the use of RNA: after having been used in medicine as micro-RNAs and tumor vaccines, the new era of anti-infectious mRNA vaccines has begun, which is currently in great development, to either improve already available, but unsatisfactory, vaccines or develop protective vaccines against infectious agents for which no preventative tools have been realized yet.

Vaccines doi: 10.3390/vaccines12121417

Authors: Zhiqiang Xie Jiangjiao Li Xue Wang Lili Huang Jinbo Gou Wei Zhang Haitao Huang Wangyang You Feiyu Wang Xiaolong Li Jinming Zhang Qiang Han Xiaomin Ma Yanxia Wang

Objectives: This study aimed to evaluate the immunogenicity and safety of a 13-valent pneumococcal polysaccharide conjugate vaccine (CRM197/TT) (PCV13i) in infants. Methods: A total of 1200 infants were randomly assigned to either the experimental PCV13i group or the control PCV13 group in a 1:1 ratio. Each group received a three-dose series of the vaccine at 2, 4, and 6 months of age, followed by a booster dose at 12–15 months. Blood samples were collected before and 30 days after both primary and booster vaccinations. The primary immunogenicity endpoints were the seropositive rate and the geometric mean concentration (GMC) of IgG antibodies against the 13 pneumococcal serotypes. The primary safety endpoint was the incidence of adverse reactions within 0–7 days and 0–30 days after vaccination. Results: Results showed that the experimental PCV13i was well tolerated, with a safety profile comparable to that of the control vaccine. Following primary vaccination, the GMCs of IgG responses against serotypes 1, 5, 6A, 6B, 14, and 18C in the experimental group were lower than those in the control group, while responses against serotypes 3, 4, 7F, 9V, 19A, 19F, and 23F were higher. The experimental group exhibited higher opsonophagocytic killing assay (OPA) geometric mean titers (GMTs) for serotypes 3, 7F, 19A, and 19F compared to the control group, while GMTs for serotypes 1, 5, 6A, and 18C were lower. Following booster vaccination, OPA GMTs of the experimental group remained higher than those of the control group for serotypes 3, 7F, and 19F, while GMTs for serotype 5 were lower. Both vaccines induced robust immune responses, with high seropositive rates and significant increases in antibody levels following vaccination. Conclusions: The experimental PCV13i demonstrated non-inferiority to the control PCV13 in terms of immunogenicity.

Vaccines doi: 10.3390/vaccines12121416

Authors: Sang-Won Kim Cheng-Dong Yu Jong-Yeol Park Xiu-Li Ma Tong Zhu Yu-Feng Li Se-Yeoun Cha Hyung-Kwan Jang Min Kang Bai Wei

Background/Objective: Duck virus hepatitis (DVH), caused by duck hepatitis A virus (DHAV), poses significant challenges to duck farming due to high mortality rates in young ducklings. Despite the widespread use of live attenuated vaccines, the genetic diversity within DHAV strains has diminished their cross-protection efficacy. This study aimed to evaluate the cross-protective efficacy of current DHAV-1 and DHAV-3 vaccines against genetically divergent wild strains. Methods: Phylogenetic analyses of the VP1 genes from DHAV-1 and DHAV-3 were conducted. Both DHAV-1 and DHAV-3 vaccines were tested in ducklings, with and without maternal-derived antibodies (MDA), through challenge trials with homologous and heterologous strains. Results: In the phylogenetic analysis, compared to vaccine strains, DHAV-1 and DHAV-3 field variant strains were classified into different genotypes. In ducklings without MDA, the DHAV-1 vaccine provided 60% survival against homologous strains by 2 days post-vaccination (DPV) and complete protection by 4 DPV, while survival rates against heterologous strains ranged from 40 to 60%. In ducklings with MDA, the DHAV-1 vaccine provided full protection with an additional vaccination for day-old ducklings against heterologous strains. The DHAV-3 vaccine conferred complete protection against both homologous and heterologous strains by 2 DPV, regardless of MDA presence. Conclusions: The DHAV-3 vaccine demonstrated robust cross-protection across genotypes, while the DHAV-1 vaccine showed limitations against genetically divergent strains. These findings highlight the necessity for genotype-matched vaccines and optimized immunization strategies to enhance protection against evolving DHAV field strains.

Vaccines doi: 10.3390/vaccines12121414

Authors: Anna-Lea Kahn Dijana Spasenoska Kouadio Daniel Ekra Soplé Ruth Coulibaly Kossia Yao Sié Kabran Kouadio Aminatou Sar Joanie Robertson

Background: Persistent inequities in access to vaccinations pose challenges for immunization programs worldwide. Innovations facilitating vaccine delivery, such as leveraging vaccine thermostability through a Controlled Temperature Chain (CTC), have emerged as a potential solution to increase coverage in low- and middle-income countries (LMICs) countries such as Côte d’Ivoire, reducing dependence on the cold chain and improving vaccine delivery efficiency. However, the added value of thermostable vaccines and their integration into national immunization programs is under-recognized by stakeholders. This consultation aimed to convene key immunization stakeholders in Côte d’Ivoire in order to examine their perceptions regarding the value of vaccine thermostability to address barriers to outreach and equity in immunization programs. Methods: A novel workshop model involving structured group discussions was used to document the viewpoints of national stakeholders representing different areas of the immunization program. They prioritized barriers undermining coverage and equity in their country and explored the potential impact of CTC on the immunization program in the context of thermostable vaccines. The vaccines discussed were for Hepatitis B, Human Papillomavirus, and Meningitis. Results: The workshop outcomes highlighted the context and vaccine-specific variation of the importance of certain barriers, emphasizing the need for tailored strategies. The barriers considered most likely to be alleviated by vaccine thermostability were under the categories of human resource management, vaccine supply and logistics, and services delivery. The least relevant category of barriers concerned demand generation. Conclusions: The consultation provided valuable insights into stakeholder perspectives, priorities, and conditions for the effective integration of thermostable vaccines, informing future product development and policy decisions to optimize vaccine delivery and address immunization challenges in LMICs.

Vaccines doi: 10.3390/vaccines12121415

Authors: Francisco Nogareda Margherita Ghiselli Martha Velandia-González Bremen de Mucio Jorge Jara Paula Couto Angel Rodriguez Marc Rondy Andrea Vicari Murat Hakan Ozturk Shoshanna Goldin Alba Vilajeliu Eva Leidman Jaymin Patel Julie Carlton Ashley L. Fowlkes Eduardo Azziz-Baumgartner Daniel Salas Peraza Alba Maria Ropero

Background: Vaccination is one of the most effective measures to prevent influenza illness and its complications. Since the 1980s, countries and territories in the Americas have progressively implemented influenza vaccination operations in high-risk priority groups—such as older adults, pregnant persons, persons with comorbidities and health workers. Methods: In this review, we present the history and progress of the seasonal influenza program in the Americas, how the program contributed to the efficient and timely roll-out of the COVID-19 vaccines during the pandemic, and how the program can be used to promote immunization operations across the life span for existing and future vaccines. Results: The influenza A(H1N1)pdm09 pandemic in 2009 and the COVID-19 pandemic in 2020–2023 underscored the importance of having a robust seasonal influenza vaccination program for pandemic preparedness and response. Overall, countries with existing seasonal influenza vaccination programs were better prepared and rolled out the delivery of COVID-19 vaccines more quickly and effectively compared to other countries where the influenza vaccination platform was weak or non-existent. Conclusions: Traditionally, national immunization programs of developing countries have been predominately focused on newborns, children younger than five years and school-aged children while often limiting their investment in effective adult vaccination programs; these programs are typically isolated to high-income countries. Countries in Latin America have been the exception, with strong influenza vaccination programs for adults regardless of national income level. The presence of functional and effective adult influenza vaccination programs can also facilitate the acceptance and uptake of other adult vaccines targeting priority groups at higher risk for severe illness or complications.

Vaccines doi: 10.3390/vaccines12121413

Authors: Hiroshi Kusunoki

This report examines the evolving role of coronavirus disease 2019 (COVID-19) vaccination in Japan, especially in light of the reduced public concern following the reclassification of COVID-19 as a Category 5 infectious disease in May 2023. With over half the population estimated to have hybrid immunity from prior infections and vaccinations, this report evaluated the necessity and frequency of additional booster doses. Despite strong recommendations from Japanese medical societies to continue vaccination, public skepticism remains owing to financial burdens, adverse reactions, and the perceived limited benefits of frequent boosters. Studies on antibody responses have revealed that individuals with hybrid immunity maintain robust protection with significantly elevated antibody titers that persist over extended periods. Case studies have indicated durable immunity among individuals who have both been vaccinated and experienced breakthrough infections, raising questions about the need for uniform booster policies. This report also discusses the newly approved replicon-type (self-amplifying) vaccines currently available only in Japan, which have generated public and professional debates regarding their efficacy and safety. A more personalized approach to vaccination that takes into account the antibody titers, prior infection history, and individual choices is recommended. Finally, this report underscores the importance of aligning vaccination policies with scientific evidence and public sentiment to optimize COVID-19 countermeasures in Japan.

Vaccines doi: 10.3390/vaccines12121412

Authors: Yao Li Yaping Long Xiangwei Ge Pengfei Zhang Tao Li Liangliang Wu Hao Fan Zhijuan Du Qiaowei Liu Yi Hu

Background: Combining radiotherapy with targeted therapy benefits patients with advanced epidermal growth factor receptor-mutated non-small cell lung cancer (EGFRm NSCLC). However, the optimal strategy to combine EGFR tyrosine kinase inhibitors (TKIs) with radiotherapy for maximum efficacy and minimal toxicity is still uncertain. Notably, EVs, which serve as communication mediators among tumor cells, play a crucial role in the anti-tumor immune response. Methods To exploit the role of EVs in the delivery of tumor antigens, we formulated a therapeutic strategy that involves the use of radiation-induced tumor-derived EVs (TEXs) loaded onto dendritic cells (DCs) as a kind of vaccine in conjunction with EGFR TKIs and assessed the efficacy and safety of this approach in the treatment of EGFRm NSCLC. Results In our study, we characterized the release of immunogens as influenced by various modes of cell death, examining the impact of different levels of cell death under diverse irradiation modalities. Our results demonstrated that a radiation mode of 6Gy*3f exhibited the most promising potential to stimulate anti-tumor immune responses. This radiotherapy fraction, combined with TKIs, showed promising results in a tumor-bearing mouse model with an EGFR mutation, although there is a risk of radiation-associated pneumonitis. Furthermore, we found that 6Gy*3f-TEXs in vitro activate DCs and promote T cell proliferation as well as cytotoxic T lymphocyte-mediated tumor cell destruction. The administration of EGFR-TKIs combined DCs loaded with 6Gy*3f-TEXs exhibited the potential to inhibit tumor growth and mitigate the risk of pneumonitis. Together, the research shows that TEXs from high-dose fractionation radiation can mature DCs and boost the killing of cytotoxic T lymphocytes. Combining these DC vaccines with Osimertinib offers a promising and safe treatment for EGFRm NSCLC.

Vaccines doi: 10.3390/vaccines12121411

Authors: Antonios Christodoulakis Izolde Bouloukaki Antonia Aravantinou-Karlatou Michail Zografakis-Sfakianakis Ioanna Tsiligianni

Background/Objectives: Healthcare professionals (HCPs) hold significant influence over public attitudes toward vaccinations. Studies suggest that HCPs are hesitant towards the coronavirus disease 2019 (COVID-19) vaccines. This hesitancy could lead to lower vaccination rates in the community. Therefore, this scoping review aimed to assess the extent of hesitancy towards COVID-19 booster doses among HCPs and identify the associated factors. Methods: A comprehensive search was conducted in the PubMed and Scopus databases from April to August 2024, using keywords related to COVID-19, vaccine hesitancy, HCPs, and booster vaccination. Studies that had been peer-reviewed, published in English after 2022, and focused on the hesitancy of the COVID-19 booster dose hesitancy among HCPs were included. Out of the 6703 studies screened, 24 studies were included. Results: Most of the HCPs have received their initial series of COVID-19 vaccinations. However, there is a lower rate of uptake for booster doses, with hesitancy rates ranging from 12% to 66.5%. Hesitancy rates varied significantly across continents, with Asia, Africa, and Europe ranging from 19.7% to 66.5%, 27% to 46.1%, 14% to 60.2%, respectively. Hesitancy was reported to be influenced by various factors, including concerns about vaccine safety, necessity, and effectiveness of these vaccines. In addition, the hesitancy regarding booster doses was also found to be influenced by factors like age, gender, profession, and previous COVID-19. Physicians, nurses, and pharmacists exhibited vaccine hesitancy rates ranging from 12.8% to 43.7%, 26% to 37%, and 26% to 34.6%, respectively. Conclusions: Our review underscores the hesitancy among HCPs towards receiving booster doses across countries around the world and explores the underlying factors. These findings provide valuable insights for the design of future pandemic vaccination programs.

Vaccines doi: 10.3390/vaccines12121410

Authors: Xiaolan Yang Yakun Sun Hongjing Gu Deyu Li Liangyan Zhang Tao Li Hui Wang

Background/Objectives: Since 2022, outbreaks of monkeypox have raised widespread concern and have been declared a public health emergency of international concern by the World Health Organization. There is an urgent need to develop a safe and effective vaccine against the monkeypox virus (MPXV). Recombinant protein vaccines play a significant role in the prevention of infectious diseases due to their high safety and efficacy. Methods: We used the A29, E8, M1, A35, and B6 proteins of MPXV as candidate antigens to generate a panel of multi-component MPXV vaccine candidates, which were administered subcutaneously to immunize mice. Results: The results showed that the vaccine candidates Mix-AEM, Mix-AEMA, Mix-AEMB, and Mix-AEMAB effectively elicited strong neutralizing antibody responses and demonstrated significant protection against vaccinia virus (VACV) infection in a murine model. The vaccine candidate Mix-AEM induced significantly higher levels of neutralizing antibodies, cellular immunity capacity, and virus clearance compared to the vaccine candidate Mix-AE (lacking M1). Single-component immunization showed that M1 induced higher levels of neutralizing antibodies than A29 and E8. These results indicated that M1 is a critical and essential antigen in the MPXV vaccine. The number of cells secreting IFN-γ was significantly increased in the Mix-AEMA and Mix-AEMAB groups compared to the A35-deficient vaccine candidates, demonstrating the important role of A35 in inducing IFN-γ secreting. In addition, the neutralizing antibodies induced by these multi-component vaccine candidates were maintained at high levels six months after the third immunization. Conclusions: In summary, this study lays the groundwork for combining antigens to develop multi-component subunit vaccines.

Vaccines doi: 10.3390/vaccines12121409

Authors: Yei Mansou Mahalakshmi Kumaran Gregory Farmer Kyle Kemp Hussain Usman David Strong George K. Mutwiri Khokan C. Sikdar

Background/objectives: Coronavirus-19 (COVID-19) vaccines represent a significant milestone in the fight against coronavirus disease. Ongoing post-marketing surveillance and research are crucial for ensuring vaccine safety and effectiveness, aiding public health planning. Methods: Our retrospective cohort study included Albertans five years and older and vaccinated with at least one dose of an approved COVID-19 vaccine between 14 December 2020 and 30 April 2022. This epidemiological study aimed to determine the incidence of reported adverse events following immunization (AEFI) in Alberta and identify associated risk factors. Results: The study included 3,527,106 vaccinated Albertans who met the study inclusion criteria. A total of 2541 individuals (72.0 per 100,000) reported an AEFI, with 2759 adverse events, most of which occurred following the first dose of vaccine and within the first week post-vaccination. Of these, 70.4% were female, and the highest incidence was in the 35–54 age group. Given that mRNA vaccines were predominantly administered across Canada, we report AEFI rates (per 100,000 doses) for the mRNA vaccine brands at 27.7 for Pfizer and 40.7 for Moderna. Allergic events were the most frequently reported AEFI, followed by adenopathy. Logistic regression analysis indicated that sex (with females at higher risk), presence of comorbidities, days to symptom onset, vaccine type (mRNA vs. mixed doses), and the number of doses were significant factors associated with an AEFI event. Conclusions: Our study provides valuable information to guide policies surrounding COVID-19 vaccination. While the risk of serious adverse events was low in the population-based sample, further research is warranted to identify and investigate other possible risk factors that are still unknown.

Vaccines doi: 10.3390/vaccines12121408

Authors: Leire Fernández-Ciriza José Luis del Pozo Nazaret Betanzos Álvaro González Alejandro Fernandez-Montero Francisco Carmona-Torre Marta Vidaurreta Silvia Carlos Gabriel Reina

Background/Objectives: The emergence of the Omicron variant has complicated COVID-19 control and prompted vaccine updates. Recent studies have shown that a fourth dose significantly protects against infection and severe disease, though long-term immunity data remain limited. This study aimed to assess Anti-S-RBD antibodies and interferon-γ levels in healthcare workers 12 months after receiving bivalent Original/Omicron BA.4-5 fourth SARS-CoV-2 vaccine. Methods: In this prospective cohort study, 549 healthcare workers were categorized by the initial vaccination schedule, with 229 individuals having received the fourth SARS-CoV-2 vaccine dose. Blood samples were collected from all participants 12 months post-vaccination. Results: Significant differences in Anti-S-RBD antibody levels were observed between those receiving a fourth dose and those who did not, while no differences were seen in interferon-γ levels. After 12 months, there were no significant differences in humoral and cellular immunity response between volunteers primoinfected or reinfected across different periods by the Omicron variant. A multivariable analysis revealed an association between high antibody levels (>6000 U/mL) and interferon-γ levels (OR: 3.13; 95% CI: 1.3–7.7; p < 0.05). Regarding primary vaccine schedules, participants vaccinated with ChAdOx1 (a single or double dose) had notably lower antibody levels compared to those who received mRNA-based vaccines. Additionally, the study shows a higher frequency of multiple infections among those with a single-dose ChAdOx1 primary schedule (OR: 6.24; 95% CI: 1.25–31.15; p < 0.01). Conclusions: Overall, mRNA-based vaccines exhibited stronger long-term immunogenicity. Repeated exposure to the Omicron variant seems to mitigate immune imprinting from the wild-type SARS-CoV-2. An association was observed between high antibody levels and a strong cellular response, although the correlation was not linear.

Vaccines doi: 10.3390/vaccines12121407

Authors: Sarah A. O’Neill Son Tran Cora Constantinescu Tony H. Truong

Background/Objectives: Vaccine hesitancy among immunocompromised patients is complex and not well understood. This study aimed to determine the rate of COVID-19 vaccine hesitancy among pediatric oncology and bone marrow transplant (BMT) patients and to understand associated factors. Methods: Parents of patients (≤18 years) with cancer or post-BMT completed the Parent Attitudes about Childhood Vaccines Survey. A COVID-19 vaccine hesitancy score (VHS-COVID) was calculated from 0 to 100 (higher scores indicating increasing hesitancy). A small group of patients (patients older than 15 years) were also surveyed directly. Results: Among 113 parent respondents, the majority were female (58%) and at least college/university educated (78%). The majority (73%) of patients had cancer (61% leukemia/lymphoma, 37% solid/CNS tumors), while 27% had received BMT for malignant and non-malignant conditions. Only 48% of patients had been vaccinated against COVID-19, compared to 88% of parents. Ineligibility due to phase of cancer/BMT treatment (27%), vaccine hesitancy (24%), and age (24%) were the top three reasons for not vaccinating against COVID-19. Only 13% of parents said they would “definitely vaccinate” if their child became eligible. VHS-COVID scores were higher for parents of patients in surveillance versus active therapy (mean 61 vs. 48; p = 0.03). Parents who had received fewer COVID-19 vaccine doses (0–1 vs. ≥2) were more hesitant toward all vaccines (p = 0.0002), COVID-19 vaccines (p = 0.0003), and influenza vaccines (p = 0.005). Conclusions: Vaccine hesitancy is common among this population and was demonstrated through beliefs (hesitancy scores) as well as vaccine uptake. Future work should focus on education targeting vaccine eligibility and engaging with vaccine hesitant families in the immunocompromised community.

Vaccines doi: 10.3390/vaccines12121406

Authors: Carmina Gallardo István Mészáros Alejandro Soler Jovita Fernandez-Pinero Erwin van den Born Alicia Simón Nadia Casado Raquel Nieto Covadonga Perez Irene Aldea Vicente Lopez-Chavarrias Eszter Göltl Ferenc Olasz Tibor Magyar Zoltán Zádori José Manuel Sánchez-Vizcaíno Marisa Arias

Background/Objectives: African swine fever virus (ASFV) is a devastating disease affecting domestic and wild suids and causing significant economic losses in the global pig industry. Attenuated modified live virus (MLV) vaccines are the most promising approaches for vaccine development. This study aimed to evaluate the safety and efficacy of four recombinant ASFV genotype II strains, derived from the non-hemadsorbing (non-HAD) attenuated isolate Lv17/WB/Rie1, through the single or simultaneous deletion of virulence-associated genes. Methods: Recombinant viruses were engineered by deleting the UK, EP402R, and EP153R genes, either individually or in combination. Four recombinant strains were evaluated for safety and efficacy in domestic pigs vaccinated intramuscularly with 102 TCID₅₀. Clinical signs, viremia, virus shedding, and antibody responses were monitored. Protection efficacy was assessed by challenging vaccinated pigs with the virulent genotype II Armenia07 strain. Additionally, a reversion-to-virulence study involving an overdose of the vaccine candidate was conducted to evaluate its stability through serial immunizations. Results: Deletion of the UK gene alone increased virulence, whereas the double deletion of EP402R and EP153R (Lv17/WB/Rie1-ΔCD) significantly enhanced safety while maintaining full protective efficacy. Vaccinated pigs exhibited reduced viremia, no virus shedding, and robust virus-specific antibody responses, achieving complete protection against Armenia07. The reversion-to-virulence study revealed potential but limited pathogenicity after multiple passages, indicating areas for improvement in vaccine stability. Conclusions: The Lv17/WB/Rie1-ΔCD strain demonstrates excellent safety and efficacy, along with potential DIVA (differentiating infected from vaccinated animals) compatibility, positioning it as a strong candidate for an ASFV MLV vaccine. Further research is needed to refine the vaccine and address the potential risks of reversion to virulence.

Vaccines doi: 10.3390/vaccines12121405

Authors: Alina Cernasev Oluwafemifola Oyedeji Cary M. Springer Tracy M. Hagemann Kenneth C. Hohmeier Kristina W. Kintziger

Background: Human papillomavirus (HPV) remains the most prevalent sexually transmitted infection in the United States (U.S.). By the age of 45, over 80% of Americans will contract HPV, which creates a significant public health concern. Despite the availability of effective vaccines, low vaccination uptake continues to be a challenge, particularly in Tennessee. Additionally, the Advisory Committee on Immunization Practices (ACIP) recently expanded recommendations for HPV vaccine usage to include adults aged 27–45, suggesting a population with the potential to experience a gap in preventative care. To understand the underlying factors that may hinder Tennesseans from receiving the HPV vaccine, we conducted a cross-sectional survey from 29 June to 17 August 2023 among adults aged 18 to 45 in Tennessee. The survey was developed and informed by a scoping review regarding the various constructs and frameworks used in vaccine hesitancy and our previous qualitative work. Using theory-based instruments and previous qualitative data, this study aimed to determine the underlying factors that may hinder Tennesseans from receiving the HPV vaccine, focusing on those adults within the recently approved age range of 27–45 years old. Methods: An Exploratory Factor Analysis of 2011 participants ultimately included five factors, which explain 70.3% of the variability. These were Benefits/Trust, Perceived Susceptibility, Attitude/Behavioral Control, Perceived Barriers, and Perceived Severity. All Cronbach alphas were greater than 0.80, indicating that each factor was reliable. Results: When stratifying by various demographics, our analysis found that race emerged as a significant factor (p = 0.002), while the interaction of race and vaccination status was not significant (p = 0.753). Black respondents had significantly lower levels of Benefits/Trust than White (p < 0.001) and Asian respondents (p = 0.030), with no significant differences between White and Asian respondents. Conclusions: These findings underscore the importance of researchers, healthcare professionals, public health officials, and policymakers in addressing these demographic differences to effectively increase vaccination rates and reduce HPV-associated cancer risks in Tennessee. Further studies are needed for targeted interventions to address these disparities.

Vaccines doi: 10.3390/vaccines12121404

Authors: Noa Feldman Michal Bitan Maya Alayev Orna Tal

Background and Objectives: In response to the COVID-19 pandemic, Israel prioritized pregnant women for vaccination, recognizing them as a high-risk group. This study aims to explore factors influencing the acceptance of Influenza, Pertussis (T-dap), and COVID-19 vaccines among pregnant women, focusing on attitudes, social norms, perceived control, and risk perceptions. Additionally, the study compares acceptance patterns between traditional vaccines and the newer COVID-19 vaccine. Methods: A prospective cohort study was conducted between December 2019 and December 2021 involving 449 predominantly Israeli pregnant women. A survey was administered to gather data on demographics, obstetric history, vaccination history, and factors influencing vaccination decisions. Results: COVID-19 vaccine uptake was the highest at 64% (202/314), followed by T-dap at 49% (221/449) and Influenza at 32% (146/449). Multivariable logistic regression showed that non-religious women and those with academic education were more likely to accept vaccines, especially the COVID-19 vaccine. Physician recommendations were the most influential factor in vaccine acceptance, while internet and media sources played a significant role in shaping COVID-19 vaccine decisions. Perceived risks varied: Whooping Cough was seen as the greatest threat to newborns, while COVID-19 posed the highest risk to mothers. Analyzing maternal and neonatal disease perception using multivariable linear regression, we found that information on maternal and neonatal Flu, Whooping Cough, and COVID-19 was significantly positively correlated with disease perception for each condition. Conclusions: Healthcare providers play a crucial role in influencing vaccine decisions, especially through personalized communication. Strategies targeting religious communities and leveraging media can help address vaccine hesitancy, ultimately improving maternal and neonatal health outcomes.

Vaccines doi: 10.3390/vaccines12121396

Authors: Atharv Athavale Anmol Gaur Nafees Ahmed Adarsh Subramaniam Jyotsna Dandotiya Sneha Raj Santosh Kumar Upadhyay Sweety Samal Anil Kumar Pandey Ramesh Chandra Rai Amit Awasthi

Background: The COVID-19 pandemic prompted unprecedented vaccine development efforts against SARS-CoV-2. India, which was one of the countries most impacted by COVID-19, developed its indigenous vaccine in addition to utilizing the ones developed by other countries. While antibody levels and neutralizing antibody titres are considered initial correlates of immune protection, long-term protection from the pathogen relies on memory B and T cells and their recall responses. In this regard, global research has primarily focused on mRNA-based vaccines. The studies on immune memory response, particularly B cell memory response induced by the vaccines given to Indians, remain relatively obscure. Methods: We assessed Receptor Binding Domain-specific memory B cells in the peripheral circulation and their ability to secrete antigen-specific antibodies among Indians vaccinated with Covaxin (BBV152), Covishield (AZD1222), Corbevax (BECOV2D), and Sputnik Light, as well as unvaccinated individuals. Results: Corbevax and Sputnik Light conferred better antibody-secreting cell (ASC) responses over time compared to other groups. Conclusions: These findings contribute to our understanding of vaccine-induced immune memory in the Indian population; providing insights that could inform future vaccine strategies.

Vaccines doi: 10.3390/vaccines12121403

Authors: Philip Hicks Tomaz B. Manzoni Jonna B. Westover Raegan J. Petch Brianne Roper Brian B. Gowen Paul Bates

Background: Severe fever with thrombocytopenia syndrome virus (SFTSV) is a recently emerged tickborne virus in east Asia with over 18,000 confirmed cases. With a high case fatality ratio, SFTSV has been designated a high priority pathogen by the WHO and the NIAID. Despite this, there are currently no approved therapies or vaccines to treat or prevent SFTS. Vesicular stomatitis virus (VSV) represents an FDA-approved vaccine platform that has been considered for numerous viruses due to its low sero-prevalence in humans, ease in genetic manipulation, and promiscuity in incorporating foreign glycoproteins into its virions. Methods: In this study, we developed a recombinant VSV (rVSV) expressing the SFTSV glycoproteins Gn/Gc (rVSV-SFTSV) and assessed its safety, immunogenicity, and efficacy in C57BL/6, Ifnar−/−, and AG129 mice. Results: We demonstrate that rVSV-SFTSV is safe when given to immunocompromised animals and is not neuropathogenic when injected intracranially into young immunocompetent mice. Immunization of wild type (C57BL/6) and Ifnar−/− mice with rVSV-SFTSV resulted in high levels of neutralizing antibodies and protection in a lethal SFTSV challenge model. Additionally, passive transfer of sera from immunized Ifnar−/− mice into naïve animals was protective when given pre- or post-exposure. Finally, we demonstrate that immunization with rVSV-SFTSV cross protects AG129 mice against challenge with the closely related Heartland bandavirus despite negligible neutralizing titers to the virus. Conclusions: Taken together, these data suggest that rVSV-SFTSV is a promising vaccine candidate for SFTSV and Heartland bandavirus with a favorable safety profile.

Vaccines doi: 10.3390/vaccines12121402

Authors: Melanie Marti Hanna Nohynek Philippe Duclos Katherine L. O’Brien Joachim Hombach

Background/Objectives: In November 1999, WHO established the Strategic Advisory Group of Experts (SAGE) on Immunization as a multidisciplinary group of experts to provide high-level recommendations on vaccines and immunization. Methods: This review provides an overview of SAGE’s work in the past 25 years. It further outlines the processes and methods currently used by SAGE and highlights some of its major achievements. Results: SAGE’s global policies have driven action toward eradication, elimination and disease control and addressed the optimization of vaccination and immunization. In total, 27 major policy positions on vaccines/vaccine-preventable diseases have guided global public health. During times of epidemics and pandemics, interim recommendations issued by SAGE have responded iteratively in real-time to provide evidence-driven response policies. SAGE is an adaptive advisory group that has modified its procedures and working approaches to meet the evolving challenges in public health and stay up-to-date with evolving scientific and guideline development standards. Conclusions: Over the last quarter century, SAGE has significantly contributed to shaping the immunization landscape. It has achieved and maintained a high level of integrity and credibility. The advisory group continues to be an authority in global public health, and its recommendations have profound implications for the health of individuals and populations across the globe.

Vaccines doi: 10.3390/vaccines12121401

Authors: Lespek Kutumbetov Balzhan Myrzakhmetova Aiganym Tussipova Gulzhan Zhapparova Talshyngul Tlenchiyeva Karina Bissenbayeva Kuanysh Zhapar Kuandyk Zhugunissov Sergazy Nurabayev Aslan Kerimbayev

The research conducted in this preclinical study assesses QazCovid-live, a live attenuated COVID-19 vaccine created in Kazakhstan, by conducting preclinical evaluations of safety, immunogenicity, and allergenicity in various animal models, including mice, rats, hamsters, and guinea pigs. The vaccine, developed by attenuating SARS-CoV-2 via numerous Vero cell passages, had no significant adverse effects in acute and subacute toxicity assessments, even at elevated dosages. Allergenicity testing indicated the absence of both immediate and delayed hypersensitivity reactions. Immunogenicity evaluations revealed strong virus-neutralizing antibody responses, especially following intranasal and intratracheal delivery. Studies on reversibility and transmission further validated the vaccine’s stability and non-pathogenicity. The data indicate that QazCovid-live is safe, immunogenic, and prepared for clinical trials, presenting a potential strategy for COVID-19 prevention.

Vaccines doi: 10.3390/vaccines12121400

Authors: Sergio A. Bucarey Lucy D. Maldonado Francisco Duarte Alejandro A. Hidalgo Leonardo Sáenz

Immunization against Gonadotropin-Releasing Hormone (GnRH) has been successfully explored and developed for the parenteral inoculation of animals, aimed at controlling fertility, reducing male aggressiveness, and preventing boar taint. Although effective, these vaccines may cause adverse reactions at the injection site, including immunosuppression and inflammation, as well as the involvement of laborious and time-consuming procedures. Oral vaccines represent an advancement in antigen delivery technology in the vaccine industry. In this study, a Salmonella enterica serovar Typhimurium (S. Typhimurium) mutant lacking the pathogenicity island 2 (S. Typhimurium ΔSPI2) was used as a vehicle and mucosal adjuvant to deliver two genetic constructs in an attempt to develop an oral immunological preparation against gonadotropin hormone-releasing hormone (GnRH). S. Typhimurium ΔSPI2 was transformed to carry two plasmids containing a modified GnRH gene repeated in tandem (GnRXG/Q), one under eukaryotic expression control (pDNA::GnRXG/Q) and another under prokaryotic expression control (pJexpress::GnRXG/Q). A group of three male BALB/c mice were orally immunized and vaccination-boosted 30 days later. The oral administration of S. Typhimurium ΔSPI2 transformed with both plasmids was effective in producing antibodies against GnRXG/Q, leading to a decrease in serum testosterone levels and testicular tissue atrophy, evidenced by a reduction in the transverse tubular diameter of the seminiferous tubules and a decrease in the number of layers of the seminiferous epithelium in the testes of the inoculated mice. These results suggest that S. Typhimurium ΔSPI2 can be used as a safe and simple system to produce an oral formulation against GnRH and that Salmonella-mediated oral antigen delivery is a novel, yet effective, alternative to induce an immune response against GnRH in a murine model, warranting further research in other animal species.

Vaccines doi: 10.3390/vaccines12121399

Authors: Worawit Louthrenoo Punsita Tangkum Nuntana Kasitanon Wanitcha Gumtorntip Poramed Winichakoon Supparat Konsamun Antika Wongthanee

Objectives: To compare disease activity and flares among different doses and types of COVID-19 vaccines in systemic lupus erythematosus (SLE) patients. Methods: SLE patients in a lupus cohort, who received at least one dose of a COVID-19 vaccine (inactivated virus, adenovirus-vectored, or mRNA vaccines) between March and October 2022 joined this study. The data regarding disease activity and flares after each dose were reviewed and compared. Results: Two hundred and one SLE patients (524 total doses) were included in this study, with 201, 199, and 124 of them receiving 1, 2, and 3 doses of a vaccine, respectively, which comprised 183, 128, and 213 doses of inactivated virus, adenovirus-vectored, and mRNA vaccines, respectively. Regardless of vaccine dose or type, there were no significant changes in SLE disease activity pre- or post-vaccination. Flares were significantly more common after the 2nd and 3rd doses than after the 1st one (20.10% and 17.74% vs. 8.96%, p = 0.001, and p = 0.010, respectively), and after inactivated virus, adenovirus-vectored and mRNA vaccinations in 11.48%, 14.84%, and 17.84% of the patients (p = ns), respectively. However, the incidence rate of flares/100 patient-months was not different. The majority of flares were severe, with renal flares being the most frequent. Renal and mucocutaneous involvement and high SLE disease activity prior to the 1st vaccine dose were independent factors that predicted flares. Conclusions: Flares after COVID-19 vaccination were not uncommon. Most of the flares were severe, mainly due to renal flares. SLE patients should have stable low disease activity prior to receiving COVID-19 vaccine in order to avoid flares.

Vaccines doi: 10.3390/vaccines12121398

Authors: Mikhail F. Vorovitch Ksenia K. Tuchynskaya Yuriy A. Kruglov Nikita S. Peunkov Guzal F. Mostipanova Ivan S. Kholodilov Alla L. Ivanova Maria P. Fedina Larissa V. Gmyl Evgeny S. Morozkin German V. Roev Lyudmila S. Karan Galina G. Karganova

Background: West Nile virus (WNV) is a rapidly growing problem worldwide. The lack of emergency treatment and a safe licensed vaccine against WNV allows the virus to cause sporadic outbreaks of human disease, including fatal cases. Formalin-inactivated vaccines have been used for a long time and have been shown to be very safe and effective, especially in susceptible populations. Methods: By adapting tick-borne encephalitis vaccine production technology, we produced a laboratory-inactivated vaccine against WNV based on the strain SHUA, isolated from humans with a lethal WNV infection in the year 2021. Results: The potential vaccine was tested for safety in vitro and in vivo in outbred SHK mice of different ages, including PCR analysis of the brains of these mice to test for the absence of viral RNA after intracerebral injection. Conclusions: The inactivated whole-virion laboratory vaccine showed 100% seroconversion and immunogenicity against WNV strain SHUA-1, isolated from a lethal human case, and provided the mice with 100% protection from disease and death.

Vaccines doi: 10.3390/vaccines12121397

Authors: Mohammad J. Nasiri Kabir Lutfy Vishwanath Venketaraman

Multidrug-resistant tuberculosis (MDR-TB) poses a significant global health threat, especially when it involves the central nervous system (CNS). Tuberculous meningitis (TBM), a severe manifestation of TB, is linked to high mortality rates and long-term neurological complications, further exacerbated by drug resistance and immune evasion mechanisms employed by Mycobacterium tuberculosis (Mtb). Although pulmonary TB remains the primary focus of research, MDR-TBM introduces unique challenges in diagnosis, treatment, and patient outcomes. The effectiveness of current treatments is frequently compromised by poor CNS penetration of anti-TB drugs and the necessity for prolonged therapy, which often involves considerable toxicity. This review explores the potential of cytokine-based adjunct immunotherapies for MDR-TBM, addressing the challenges of balancing pro-inflammatory and anti-inflammatory signals within the CNS. A central focus is the prospective role of glutathione, not only in reducing oxidative stress but also in enhancing host immune defenses against Mtb’s immune evasion strategies. Furthermore, the development of vaccines aimed at upregulating glutathione synthesis in macrophages represents a promising strategy to bolster the immune response and improve treatment outcomes. By integrating glutathione and innovative vaccine approaches into MDR-TBM management, this review proposes a comprehensive strategy that targets Mtb directly while supporting immune modulation, with the potential to enhance patient outcomes and reduce treatment related adverse effects. We underscore the urgent need for further research into adjunctive therapies and immunomodulatory strategies to more effectively combat MDR-TBM.

Vaccines doi: 10.3390/vaccines12121395

Authors: Ana Pereira Cláudia Pinho Adriana Oliveira Rui Santos Miguel Felgueiras João P. Martins

Background: The World Health Organization estimates that currently available vaccines prevent 2 to 3 million deaths worldwide each year. Preventing infectious diseases is an important public health priority to ensure healthy ageing and improve quality of life. This study’s aim is to identify the best strategies to increase vaccination coverage in the elderly. Methods: A systematic review and meta-analysis were carried out, including a bibliographic search in the PubMed and Scopus databases. Studies in older people (60 years or older) on any type of intervention aimed at increasing vaccination coverage were included. The effect of the intervention was measured using the odds ratio (OR). Results: After applying the selection criteria, 20 studies were identified: 17 on influenza vaccines and 3 on other vaccines. Educational strategies obtained an OR = 1.63 (95% CI: 1.22–2.19, I2 = 0.59). Medical counselling obtained an OR = 3.13 (95% CI: 0.60–16.37, I2 = 0.95). Writing strategies obtained an OR = 1.14 (95% CI: 0.99–1.32, I2 = 0.93). Few studies reported the effect of free vaccination. Conclusions: The educational strategies proved to be more effective than the others in this study. Free vaccination and age may have important roles. Further studies are needed as research in this area remains limited.

Vaccines doi: 10.3390/vaccines12121394

Authors: Christopher S. Semancik Hilary S. Whitworth Matt A. Price Heejin Yun Thomas S. Postler Marija Zaric Andrew Kilianski Christopher L. Cooper Monica Kuteesa Sandhya Talasila Nina Malkevich Swati B. Gupta Suzanna C. Francis

Background/Objectives: Orthoebolaviruses and orthomarburgviruses are filoviruses that can cause viral hemorrhagic fever and significant morbidity and mortality in humans. The evaluation and deployment of vaccines to prevent and control Ebola and Marburg outbreaks must be informed by an understanding of the transmission and natural history of the causative infections, but little is known about the burden of asymptomatic infection or undiagnosed disease. This systematic review of the published literature examined the seroprevalence of antibodies to orthoebolaviruses and orthomarburgviruses in sub-Saharan Africa. Methods: The review protocol was registered on PROSPERO (ID: CRD42023415358) and previously published. Eighty-seven articles describing 85 studies were included, of which seventy-six measured antibodies to orthoebolaviruses and forty-one measured antibodies to orthomarburgviruses. Results: The results highlight three central findings that may have implications for vaccine development and deployment. First, substantial antibody seropositivity to Ebola virus (EBOV) and Sudan virus (SUDV) was observed in populations from outbreak-affected areas (≤33% seroprevalence among general populations; ≤41% seroprevalence among healthcare workers and close contacts of disease cases). Second, antibody seropositivity to EBOV, SUDV, and Marburg virus (MARV) was observed among populations from areas without reported outbreaks, with seroprevalence ranging from <1 to 21%. Third, in Central and East Africa, MARV antibody seroprevalence was substantially lower than EBOV or SUDV antibody seroprevalence, even in outbreak-affected areas and in populations at a moderate or high risk of infection (with MARV seroprevalence mostly ranging from 0 to 3%). Conclusions: Whilst gaps remain in our understanding of the significance of antibody seropositivity in some settings and contexts, these findings may be important in considering target indications for novel filovirus vaccines, in defining study designs and strategies for demonstrating vaccine efficacy or effectiveness, and in planning and evaluating vaccine deployment strategies to prevent and control outbreaks.

Vaccines doi: 10.3390/vaccines12121393

Authors: Justyna Grudziąż-Sękowska Kuba Sękowski Zuzanna Grześczyk-Nojszewska Agnieszka Kamińska Radosław Sierpiński Janusz Ostrowski Jarosław Pinkas Mateusz Jankowski

Objectives: Herpes zoster (HZ), caused by varicella zoster virus reactivation, affects a significant portion of the population, leading to substantial morbidity. Vaccination is highly effective in preventing HZ, yet awareness and uptake remain low. This study assessed awareness and willingness to vaccinate against HZ in Poland following the introduction of a reimbursement policy. Methods: A nationwide cross-sectional survey (September 2024) using a computer-assisted web interview (CAWI) method collected data from 1137 adults. Factors associated with HZ vaccine awareness and willingness were analyzed using logistic regression models. Results: Only 47% of respondents reported awareness of the HZ vaccine. Television was the primary information source (52%). Factors associated with awareness included chronic disease status (aOR = 1.35, 1.02–1.80, p = 0.04). Willingness to vaccinate was reported by 63.7% of eligible participants, with factors such as the absence of children (aOR = 1.30, 1.01–1.69, p = 0.04) and moderate financial status (aOR = 1.51, 1.04–2.18, p = 0.03) being associated with higher willingness. Conclusions: Significant gaps exist in public awareness and willingness to vaccinate against HZ in Poland. Multifaceted strategies, including targeted media campaigns, enhanced physician engagement and improved access, are needed to increase vaccination rates.

Vaccines doi: 10.3390/vaccines12121392

Authors: Kyu-Ri Kang Pan-Kyeom Kim Kyung-Min Jo Jin-Young Jang Hyun Mi Kang Jin-Han Kang

Background: Influenza remains a significant public health challenge, with vaccination being a substantial way to prevent it. Cell-cultured influenza vaccines have emerged to improve on the drawbacks of egg-based vaccines, but there are few studies focusing on T cell immunity with both types of vaccines. Therefore, we studied the following 2022–2023 seasonal influenza vaccines with a standard dose and high dose: cell-based (C_sd and C_hd) and egg-based (E_sd and E_hd) vaccines. Methods: Along with a saline control group, C_sd, C_hd, E_sd, and E_hd vaccines were administered to BALB/c mice, followed by a challenge with the A/Victoria/2570/2019 (H1N1) strain. Results: After the challenge, four out of five mice in the saline group died by day 7 post-infection (P.I.). None of the vaccinated groups experienced over 20% weight loss or any deaths. On day 7 P.I., the lung viral load in the saline group (mean log value of 4.17) was higher than that in the vaccinated groups, with the C_sd group showing the lowest viral load (mean log value of 3.47). The C_sd group showed a significantly high response in macrophage 1 (M1), IFN-γ+ T cells, and tissue-resident memory (TRM) T cells compared with the E_sd group on day 2 P.I. These M1, IFN-γ+ T cells, and TRM cells showed similar trends (p < 0.01). In terms of humoral immunity, only the E_hd group showed HAI titers above 40 for all four strains before and after the challenge. Conclusions: The high levels of T cells in the cell-cultured vaccines suggest, pending further real-world research, that these vaccines may offer advantages.

Vaccines doi: 10.3390/vaccines12121391

Authors: Bart Jacobs Isabel Leroux-Roels Jacques Bruhwyler Nicola Groth Gwenn Waerlop Yorick Janssens Jessika Tourneur Fien De Boever Azhar Alhatemi Philippe Moris Alexandre Le Vert Geert Leroux-Roels Florence Nicolas

Background/Objectives: In a Phase 2a, double-blind, placebo-controlled study including healthy participants aged 18–55 years, OVX836, a nucleoprotein (NP)-based candidate vaccine, previously showed a good safety profile, a robust immune response (both humoral and cellular) and a preliminary signal of protection (VE = 84%) against PCR-confirmed symptomatic influenza after a single intramuscular dose of 180 µg, 300 µg or 480 µg. Methods: Using the same methodology, we confirmed the good safety and strong immunogenicity of OVX836 at the same doses in older adults (≥65 years), a key target population for influenza vaccination. Results: Significant humoral (anti-NP IgG) and cellular (interferon gamma (IFNγ) spot-forming cells per million peripheral blood mononuclear cells and specific CD4+ IFNγ+ T-cells) immune responses were observed at the three dose levels, without clear dose–response relationship. T-cell responses were shown to be highly cross-reactive against various influenza A strains, both seasonal and highly pathogenic avian strains. We also evaluated the effect of sex (stronger immune response in females) and age (stronger immune response in young adults) on the immune response to OVX836 after adjustment based on the pre-vaccination immune status. Conclusions: The results obtained with OVX836 lay the groundwork for a future placebo-controlled, field proof of concept efficacy Phase 2b trial.

Vaccines doi: 10.3390/vaccines12121390

Authors: Angela Stufano Valentina Schino Guglielmo Lucchese

The immune response to SARS-CoV-2 infection is highly complex, involving a dynamic interplay between the innate and adaptive immune systems [...]

Vaccines doi: 10.3390/vaccines12121389

Authors: Mariia I. Vasilieva Rimma O. Shatalova Kseniia S. Matveeva Vadim V. Shindyapin Ekaterina Minskaia Roman A. Ivanov Daniil V. Shevyrev

Preventive medicine has proven its long-term effectiveness and economic feasibility. Over the last century, vaccination has saved more lives than any other medical technology. At present, preventative measures against most infectious diseases are successfully used worldwide; in addition, vaccination platforms against oncological and even autoimmune diseases are being actively developed. At the same time, the development of medicine led to an increase in both life expectancy and the proportion of age-associated diseases, which pose a heavy socio-economic burden. In this context, the development of vaccine-based approaches for the prevention or treatment of age-related diseases opens up broad prospects for extending the period of active longevity and has high economic potential. It is well known that the development of age-related diseases is associated with the accumulation of senescent cells in various organs and tissues. It has been demonstrated that the elimination of such cells leads to the restoration of functions, rejuvenation, and extension of the lives of experimental animals. However, the development of vaccines against senescent cells is complicated by their antigenic heterogeneity and the lack of a unique marker. In addition, senescent cells are the body’s own cells, which may be the reason for their low immunogenicity. This mini-review discusses the mechanisms of central and peripheral tolerance that may influence the formation of an anti-senescent immune response and be responsible for the accumulation of senescent cells with age.

Vaccines doi: 10.3390/vaccines12121388

Authors: Jayachandra Reddy Nakkala Yibo Li Labone Akter Xinliang Kang Xinyuan Chen

The authors would like to make the corrections described below to the published paper [...]

Vaccines doi: 10.3390/vaccines12121387

Authors: Honglei Wang Wenhai Feng

Porcine reproductive and respiratory syndrome (PRRS), characterized by reproductive failures in breeding pigs and respiratory diseases in growing pigs, is a widespread and challenging disease. The agent, PRRSV, is a single-strand RNA virus that is undergoing continuous mutation and evolution, resulting in the global spread of multiple strains with different genetic characteristics and variable antigens. There are currently no effective measures to eradicate PRRS, and vaccination is crucial for controlling the disease. At present, various types of vaccine are available or being studied, including inactivated vaccines, modified live virus (MLV) vaccines, vector vaccines, subunit vaccines, DNA vaccines, RNA vaccines, etc. MLV vaccines have been widely used to control PRRSV infection for more than 30 years since they were first introduced in North America in 1994, and have shown a certain efficacy. However, there are safety and efficacy issues such as virulence reversion, recombination with field strains, and a lack of protection against heterologous strains, while other types of vaccine have their own advantages and disadvantages, making the eradication of PRRS a challenge. This article reviews the latest progress of these vaccines in the prevention and control of PRRS and provides scientific inspiration for developing new strategies for the next generation of PRRS vaccines.

Vaccines doi: 10.3390/vaccines12121386

Authors: Justin C. Smith Prabhu S. Arunachalam Traci H. Legere Lisa A. Cavacini Eric Hunter Bali Pulendran Rama R. Amara Pamela A. Kozlowski

Background: A goal of mucosal human immunodeficiency virus type 1 (HIV-1) vaccines is to generate mucosal plasma cells producing polymeric IgA (pIgA)-neutralizing antibodies at sites of viral entry. However, vaccine immunogens capable of eliciting IgA neutralizing antibodies (nAbs) that recognize tier 2 viral isolates have not yet been identified. Methods: To determine if stabilized native-like HIV-1 envelope (Env) trimers could generate IgA nAbs, we purified total IgA and IgG from the banked sera of six rhesus macaques that had been found in a previous study to develop serum nAbs after subcutaneous immunization with BG505.664 SOSIP and 3M-052 adjuvant, which is a TLR7/8 agonist. The neutralization of autologous tier 2 BG505 T332N pseudovirus by the IgA and IgG preparations was measured using the TZM-bl assay. Anti-SOSIP binding antibodies (bAbs) were measured by ELISA. Results: The IgG samples were found to have significantly greater levels of both nAb and bAb. However, after normalizing the nAb titer relative to the concentration of bAb, SOSIP-specific IgA purified from 2/6 animals was found to neutralize just as effectively as SOSIP-specific IgG, and in 3/6 animals, neutralization by the specific IgA was significantly greater. The more potent neutralization by IgA in these three animals was associated with a higher percentage of anti-SOSIP J chain-bound (polymeric) antibody. Conclusions: The parenteral vaccination of nonhuman primates with BG505.664 SOSIP generates HIV-1 tier 2 IgA nAbs in serum, including SOSIP-specific polymeric IgA, which appears to neutralize more efficiently than monomeric IgA or IgG. Mucosal delivery of this SOSIP or other stable Env trimers could generate locally synthesized polymeric IgA nAbs in mucosal tissues and secretions.

Vaccines doi: 10.3390/vaccines12121385

Authors: Sana Malik K. Olivia Mock Rose Martillotti Giuseppina Caravella Xicheng Zhou Matthew Mbamelu Kathleen H. Scarbrough

Human papillomavirus (HPV) is the most common sexually transmitted infection and plays a significant role in cervical, penile, anal, vaginal, vulvar, and oropharyngeal cancers as well as non-cancerous genital warts and genital dysplasia. In the United States, there are approximately 46,000 new HPV-related cancers a year. There is an effective vaccine to prevent over 90% of these cancers and other HPV-related diseases; however, those that are aged 18–26 have the lowest vaccine rates among eligible age groups. The objective of this study was to examine student knowledge and perceptions about HPV vaccine hesitancy in university students and their notions of barriers and facilitators for HPV vaccine uptake. We aimed to identify components for an evidence-based community-oriented educational intervention to increase HPV vaccination uptake. The researchers recorded 10 focus groups featuring students from a Northeastern United States university, aged 18–26, which were analyzed using grounded theory and inductive thematic analysis to identify recurring themes. The participants mentioned many barriers and facilitators for attaining the HPV vaccine, with health literacy being prominent for both. They demonstrated some knowledge of what HPV is and ways to avoid it. They also expressed a desire for further information and felt that the way in which this information is presented to the public is vital for increasing vaccine uptake and designing future interventions. In order to increase HPV vaccination rates in the general population and overcome barriers such as family, religious, and cultural values, it is important to emphasize the link between HPV and cancer and its preventative benefits.

Vaccines doi: 10.3390/vaccines12121384

Authors: Wenhao Zhou Xiaojun Lu Feng Tian Qianming Luo Weihang Zhou Siyuan Yang Wenxuan Li Yongjun Yang Minfeng Shi Tie Zhou

Prostate cancer is a prevalent cancer in elderly men, and immunotherapy has emerged as a promising treatment approach in recent years. The aim of immunotherapy is to stimulate the body’s immune system to target and destroy cancer cells. Cancer vaccines that are highly specific, safe, and capable of creating long-lasting immune responses are a key focus in cancer immunotherapy research. Despite progress in clinical trials showing positive results, the practical use of cancer vaccines still encounters various obstacles. The complexity of the immune microenvironment and variations in the immune systems of individual patients have hindered the progress of research on prostate cancer vaccines. This review examines the history and mechanisms of cancer vaccines, summarizes recent clinical research findings, and explores future directions in the development of prostate cancer vaccines.

Vaccines doi: 10.3390/vaccines12121383

Authors: Elsemieke te Linde Marjolein P. M. Hensgens Albert M. Vollaard Annelies Verbon Anke H. W. Bruns

Background: In recent decades, the number of immunocompromised patients (ICPs) has increased significantly. ICPs have an impaired immune system, making them susceptible to complicated infections. To protect them from infections, ICPs are eligible to receive several medically indicated vaccines. To obtain insight into the uptake of these medically indicated vaccines, we determined the coverage of these vaccines in ICPs. Methods: This observational cohort study was conducted at the University Medical Centre Utrecht, the Netherlands, from September 2021 to April 2022. All adult ICPs admitted for COVID-19 were asked to complete a questionnaire on their vaccination history (pneumococcal, herpes zoster, human papillomavirus vaccination, influenza, and COVID-19 vaccines) and history of vaccine-preventable infections. In addition, patients’ vaccination history was reviewed in medical files. Results: A total of 115 patients completed the questionnaire and were included. Although all patients had an indication for pneumococcal vaccination, only 22 received it (19%). Coverage for herpes zoster was low (1%, 1/106 eligible patients). Coverage for human papillomavirus vaccination (HPV) was also low (40%, two out of five eligible patients). In contrast, 92% of patients received vaccination against SARS-CoV-2, and 77% of patients received seasonal influenza vaccination. Conclusions: Although coverage for influenza and COVID-19 vaccination was high in ICPs, coverage for other medically indicated vaccines was low. Identifying which factors contributed to high COVID-19 and influenza vaccine uptake can help to improve vaccination rates for the other recommended vaccines. Clear guidelines for clinicians and the removal of organizational obstacles are needed to improve vaccination coverage.

Vaccines doi: 10.3390/vaccines12121382

Authors: Ziqi Cheng Junfeng Ma Chenyan Zhao

Influenza poses a significant global health challenge due to its rapid mutation and antigenic variability, which often leads to seasonal epidemics and frequent outbreaks. Traditional vaccines struggle to offer comprehensive protection because of mismatches with circulating viral strains. The development of a broad-spectrum vaccine is therefore crucial. This paper explores the potential of mRNA vaccine technology to address these challenges by providing a swift, adaptable, and broad protective response against evolving influenza strains. We detail the mechanisms of antigenic variation in influenza viruses and discuss the rapid design and production, enhanced immunogenicity, encoding of multiple antigens, and safety and stability of mRNA vaccines compared to traditional methods. By leveraging these advantages, mRNA vaccines represent a revolutionary approach in influenza prevention, potentially offering broad-spectrum protection and significantly improving global influenza management and response strategies.

Vaccines doi: 10.3390/vaccines12121381

Authors: Amornphat Kitro Wachiranun Sirikul Chanachai Polpitakchai Jinjuta Panumasvivat Ranchana Yamsiri Pacharee Tasena Chutima Punyaphab Chaiy Rungsiyakull Ratana Sapbamrer Penprapa Siviroj Kriengkrai Srithanaviboonchai

Background: The emergence of new COVID-19 variants continues to affect healthcare workers (HCWs) and vulnerable populations in the post-pandemic era. This study aims to assess the willingness, perceptions, and factors associated with booster COVID-19 vaccine uptake in this context. Methods: A cross-sectional study was conducted between October 2023 and May 2024 among Thai adults (>20 years old) in Chiang Mai, Northern Thailand. Participants included HCWs and patients with chronic medical conditions. People who had received a monovalent XBB-derived booster vaccine were excluded. Results: Data related to a total of 811 participants were analyzed, with 328 from the vulnerable group and 483 HCWs. Willingness to receive the booster was similar in both groups (43.3% in HCWs, 45.0% in the vulnerable group). Low-risk perception (59.6%–83.5%), minimal impact on daily life (60.4%–62.9%), and doubts about booster efficacy (75.9%–81.4%) were prevalent negative thoughts toward the booster. Having received a flu vaccine (aOR 2.1), concerns about the impact on life of COVID-19 (aOR 1.8), and beliefs in booster safety (aOR 1.8) and vaccine effectiveness against severe disease (aOR 2.7) were associated with increased willingness. Conclusions: Only 44% of participants were willing to receive a COVID-19 booster. Policymakers can use these insights to develop strategies to increase vaccine uptake in the post-pandemic era.

Vaccines doi: 10.3390/vaccines12121380

Authors: Siobhan M. Wong King Yuen Emily J. Doucette Caitlin Ford Madison M. Fullerton Ginamaria Vetro Amanda Koyama Jia Hu Cora Constantinescu

Background/Objectives: As the newcomer population in Canada continues to grow, we aimed to collaborate with newcomer families arriving in an urban center in Alberta, Canada to identify strategies to overcome identified barriers newcomers face in obtaining routine childhood vaccines (RCVs). Methods: We recruited newcomers living in Calgary, Alberta to participate in a workshop utilizing the Nominal Group Technique (NGT) to develop solutions addressing barriers to obtaining RCVs. Ranking exercises helped identify the top-proposed interventions based on perceived impact and feasibility for implementation. Based on the identified need for translated vaccine resources, infographics on school-based vaccines were developed. The infographics were pilot-tested in a first-language focus group before the final product was translated into 10 different languages. Results: Consensus from 15 NGT workshop participants identified five key solutions to facilitate obtaining routine childhood immunizations: (1) Increasing access to reliable vaccine information; (2) Ensuring vaccine information and healthcare services are available in different languages; (3) Increasing vaccine appointment availability and optimizing the booking system for ease of navigation; (4) Increasing the role of family doctors in vaccine counseling and administration; (5) Streamlining vaccine record tracking. We developed infographics on the vaccines children in Alberta can receive through school-based vaccine programs and these were pilot-tested with 16 participants in a first-language (Arabic) focus group. Conclusions: The collaborative and iterative process of solution development with newcomers provided a platform for knowledge translation through the development of educational resources on school-based vaccines, addressing the information barrier that newcomers identified when accessing RCVs.

Vaccines doi: 10.3390/vaccines12121379

Authors: Jia Li Ruowen Pan Fengyi Yue Tie Gao Xiaohong Wu Leitai Shi Yunpeng Wang Danhua Zhao Zhaohui Lan Hongxu Chen Qiang Ye Shouchun Cao

Background: The Vero cell rabies vaccine is currently the most widely used human rabies vaccine. However, owing to the presence of residual host cell DNA (HCD) in the final product and the potential tumorigenicity of the DNA of high-passage Vero cells, the WHO not only sets a limit on the number of times cells used in production can be passaged, but also imposes strict requirements on the amount of residual HCD in the final vaccine product. Objectives: To systematically reduce the HCD level in the final vaccine product, multiple purification steps are included in the vaccine production process. This study investigated the effectiveness of key production steps in antigen recovery and DNA removal. Methods: The residual HCD fragment content and size distribution were detected using fluorescence quantitative PCR (qPCR) and capillary gel electrophoresis (CGE), and the rabies virus glycoprotein antigen content was detected using enzyme-linked immunosorbent assay (ELISA). The antigen recovery rate and HCD removal rate in each key process were calculated to evaluate the scientific basis and effectiveness of each production step. Additionally, the stability of the process was studied using multiple commercial batches of the product. Results: The results revealed that the total antigen recovery rate in the production process described in this report was no less than 8.5%, and the effective removal rate of residual HCD was not lower than 99.99%. Moreover, the amount of residual HCD in the final product was far below the quality standard of 2 ng/dose, and most of the residual HCD fragments were smaller than 200 bp. The results of the process stability studies on multiple commercial batches showed that the bulk human rabies vaccine produced by this process had excellent safety and efficacy and that the production process was stable and thus suitable for large-scale batch production. Conclusions: The production process described in this study achieved effective recovery of viral antigens and efficient removal of residual HCD, and the process was stable and controllable, enabling the continuous and stable production of vaccine products that meet WHO recommendations and the relevant requirements of the current edition of the Chinese Pharmacopeia. In addition, this study provides theoretical guidance for optimizing the vaccine production process.

Vaccines doi: 10.3390/vaccines12121378

Authors: Barbara Platschek Fritz Boege

Background/Objectives: Clinical studies show that SARS-CoV-2 vaccination sometimes entails a severe and disabling chronic syndrome termed post-acute-COVID-19-vaccination syndrome (PACVS). PACVS shares similarities with long COVID. Today, PACVS is still not officially recognised as a disease. In contrast, long COVID was registered by health authorities in December 2021. Here, we address possible reasons for that discrepancy. Methods: We analyse whether common symptoms of PACVS have been registered by European pharmacovigilance as adverse vaccination reactions and which consequences have been drawn thereof. Results: (i) PACVS is distinguished from normal vaccination reactions solely by prolonged duration. (ii) Symptom duration is poorly monitored by post-authorisation pharmacovigilance. (iii) PACVS-specific signals were faithfully recorded by pharmacovigilance systems but have not prompted appropriate reactions of health authorities. (iv) The most widely applied SARS-CoV-2 mRNA-vaccine has been modified after roll-out without renewed phase III evaluation; the modification has increased DNA contaminations suspected to extend the spectrum of adverse events. (v) Crossing of pharmacovigilance data with corresponding estimates of applied vaccine doses suggest a PACVS prevalence of 0.003% in the general population. In contrast, occupational surveillance studies suggest a PACVS prevalence of 0.9% in young and middle-aged persons. Conclusions: (a) Denial of official recognition of PACVS is unjustified. (b) PACVS seems to target preferentially young and middle-aged persons. (c) Without official disease recognition, access to public healthcare and welfare services is made difficult for PACVS-affected persons, which creates considerable socio-economic problems. (d) Without official disease recognition, development and evaluation of PACVS therapies is impaired.

Vaccines doi: 10.3390/vaccines12121377

Authors: Sirine Abidi Aurora Elhazaz Fernandez Nicole Seehase Lina Hanisch Alexander Karlas Volker Sandig Ingo Jordan

Background/Objectives: Poxviruses are large DNA viruses that replicate in the host cytoplasm without a nuclear phase. As vaccine vectors, they can package and express large recombinant cassettes from different positions of their genomic core region. We present a comparison between wildtype modified vaccinia Ankara (MVA) and isolate CR19, which has significantly expanded inverted terminal repeats (ITRs). With this expansion, a site in wildtype MVA, called deletion site (DS) IV, has been duplicated at both ends of the genome and now occupies an almost central position in the newly formed ITRs. Methods: We inserted various reporter genes into this site and found that the ITRs can be used for transgene expression. However, ITRs are genomic structures that can rapidly adapt to selective pressure through transient duplication and contraction. To test the potential utility of insertions into viral telomers, we inserted a factor from the cellular innate immune system that interferes with viral replication as an example of a difficult transgene. Results: A site almost in the centre of the ITRs can be used for transgene expression, and both sides are mirrored into identical copies. The example of a challenging transgene, tetherin, proved to be surprisingly efficient in selecting candidate vectors against the large background of parental viruses. Conclusions: Insertion of transgenes into ITRs automatically doubles the gene doses. The functionalisation of viruses with tetherin may accelerate the identification and generation of recombinant vectors for personalised medicine and pandemic preparedness.

Vaccines doi: 10.3390/vaccines12121376

Authors: Jing Wang Jian Du Yan Liu Yuyang Xu Jiayin Han Xuechao Zhang

Objectives: This study aimed to evaluate the safety profile of the recombinant zoster vaccine (RZV) after its marketing in China. Methods: We present a descriptive analysis and safety signal assessment of adverse events following immunization (AEFI) associated with RZV between September 2020 and December 2023. The descriptive data collected includes demographic characteristics and the classification of characteristics of AEFI cases, while vaccine safety signal assessment was evaluated using the reporting odds ratio (ROR). Results: In total, we documented 275 AEFI cases following RZV vaccination, with a reporting rate of 76.22/10,000 doses administered. Notably, only one case was classified as serious, and the reporting rates were significantly higher among females, individuals aged 50–59 years, and those residing in rural areas. Furthermore, the reporting rate for the first dose exceeded that for the second dose. Among the reported AEFI cases, 98.91% were attributed to vaccine product-related reactions, and 97.45% were initially reported by either the vaccine recipient or their guardians. The interval between vaccination and symptom onset was predominant within 3 d after vaccination. The disproportionality analysis identified five positive signals—fever (37.5–38.5 °C), injection site reactions greater than 5 cm, pain, Henoch Schönlein purpura (HSP), and swelling—which suggests a stronger association with the RZV than the expected threshold. Conclusion: In summary, RZV demonstrated a favorable safety profile. However, continued monitoring and research on the long-term safety implications of RZV are needed.

Vaccines doi: 10.3390/vaccines12121374

Authors: Ashley Hedrick McKenzie Lara S. Savas Ross Shegog Dale S. Mantey Erica L. Frost Paul Gerardo Yeh C. Mary Healy Stanley Spinner L. Aubree Shay Sharice M. Preston Sally W. Vernon

Background/objectives: Pediatrician recommendations are highly influential in parents’ decisions to vaccinate their children against HPV. Unqualified, presumptive, and bundled recommendations (UPBRs) are associated with increased HPV vaccine uptake and are considered best practice. This study analyzes pediatricians’ self-reported data to assess changes in UPBR use and the psychosocial determinants of UPBR use as a result of the implementation of a multi-level intervention, the Adolescent Vaccination Program (AVP). Methods: We surveyed pediatricians across 51 clinics in the Houston area. Baseline surveys (n = 137) were distributed in 2015, and follow-ups (n = 120) in 2019. Results: Pediatrician UPBR use significantly increased as a result of AVP implementation. Change in the provider belief that it is necessary to tell parents that HPV vaccination is not required for public school attendance significantly predicted UPBR use at follow up. This belief was also a significant mediator of increased use of UPBRs at follow-up. Conclusions: AVP was successful in increasing pediatricians’ use of UPBRs. Change in UPBR use is related to one critical psychosocial determinant: beliefs about communication regarding the non-mandatory nature of HPV vaccination for school enrollment. HPV vaccine promotion efforts should devote focus to changing pediatricians’ beliefs about the necessity of disclosing the non-mandatory nature of HPV vaccination for school attendance.

Vaccines doi: 10.3390/vaccines12121375

Authors: Sharmeen Nishat Md Kamal Hossain Geraud Valentin Farzana Hossain Shanika Gamage Katherine A. Wall Peter R. Andreana

Background/Objectives: The MHCII-dependent, CD4+ T-cell zwitterionic polysaccharide PS A1 has been investigated as a promising carrier for vaccine development because it can induce an MHCII-dependent CD4+ response towards a variety of tumor-associated carbohydrate antigens (TACAs). However, PS A1 cannot elicit cytotoxic T lymphocytes through MHCI, which may or may not hamper its potential clinical use in cancer, infectious and viral vaccine development. This paper addresses PS A1 MHCI independence through the introduction of an MHCI epitope, the poliovirus (PV) peptide, to establish an MHCI- and MHCII-dependent vaccine. Methods: We synthesized a glycopeptide construct targeting the Thomsen-nouveau TACA (Tn-PV-PS A1) and a control Tn-PV peptide. C57BL/6 mice were immunized with both constructs, and the resulting T-cells were extracted from spleens. Results: Through cell proliferation assays, we show that Tn-PV-PS A1 elicits a robust CD4+ and CD8+ immune response. The resulting cytotoxic T lymphocytes are specific towards Tn-PV and trigger cell lysis of Tn-expressing EL4 cells. Conclusions: This study confirms PV-PS A1 as a robust MHCI- and MHCII-dependent carrier. This is the first report of MHCI dependence in a zwitterionic polysaccharide.

Vaccines doi: 10.3390/vaccines12121373

Authors: Paul F. Gillespie Yanjie Wang Kuo Yin Emily Groegler Nicholas Cunningham Alyssa Q. Stiving Jessica Raffaele Natalia Marusa Christopher M. Tubbs John W. Loughney Michael A. Winters Richard R. Rustandi

Background/Objectives: Host cell protein (HCP) content is a major attribute for biological and vaccine products that must be extensively characterized prior to product licensure. Enzyme Linked Immunosorbent Assay (ELISA) and Mass Spectrometry (MS) are conventional methods for quantitative host cell protein analysis in biologic and vaccine products. Both techniques are usually very tedious, labor-intensive, and challenging to transfer to other laboratories. In addition, the ELISA methodology requires 2D SDS PAGE and 2D western blot antibody reagent validation to establish reagent coverage. This reagent coverage provides a rather weak link that is currently accepted, as the western blot is run under denaturing conditions and the ELISA is run under native conditions. Simple Western™ is a relatively new, automated, capillary western blot-based technology that allows for the separation, blotting, and detection of proteins. But, unlike traditional western blots, Simple Western™ is quantitative, allowing for the quantification of HCP content in biologic and vaccine samples. Antibody reagent validation is much more straightforward, as the reagent coverage can be directly linked between the 2D methodology and Simple Western™, as they are both run under denatured and reduced conditions. Methods: Herein we describe the development of a capillary western blot method to quantify the HCP content in samples generated using a Vero cell line for the production of an investigational live virus vaccine candidate (V590) for Coronavirus Disease-2019 (COVID-19). The HCP content in COVID-19 vaccine samples was evaluated using three methods: the new capillary western, the gold standard ELISA, and SDS-PAGE. Results/Conclusions: Strong agreement was observed in the HCP content data between the capillary western and SDS PAGE methods, whereas the ELISA HCP data were outliers, suggesting that the capillary western is generating HCP concentrations closer to the true concentration. This is the first report of using capillary western technology in analyzing HCP in vaccine samples.

Vaccines doi: 10.3390/vaccines12121372

Authors: Lixing Wang Branka Vulesevic MariaLuisa Vigano Alia As’sadiq Kristina Kang Cristina Fernandez Suzanne Samarani Aslam H. Anis Ali Ahmad Cecilia T. Costiniuk

HIV causes intense polyclonal activation of B cells, resulting in increased numbers of spontaneously antibody-secreting cells in the circulation and hypergammaglobulinemia. It is accompanied by significant perturbations in various B cell subsets, such as increased frequencies of immature/transitional B cells, activated memory B cells, atypical memory B cells, short-lived plasmablasts and regulatory B cells, as well as by decreased frequencies of resting memory and resting naïve B cells. Furthermore, both memory and antigen-inexperienced naïve B cells show exhausted and immune-senescent phenotypes. HIV also drives the expansion and functional impairment of CD4+ T follicular helper cells, which provide help to B cells, crucial for the generation of germinal center reactions and production of long-lived plasma and memory B cells. By suppressing viral replication, anti-retroviral therapy reverses the virus-induced perturbations and functional defects, albeit inadequately. Due to HIV’s lingering impact on B cells, immune senescence and residual chronic inflammation, people with HIV (PWH), especially immune non-responders, are immunocompromised and mount suboptimal antibody responses to vaccination for SARS-CoV-2. Here, we review how functionally and phenotypically distinct B cell subsets are induced in response to a vaccine and an infection and how HIV infection and anti-retroviral therapy (ART) impact them. We also review the role played by HIV-induced defects and perturbations in B cells in the induction of humoral immune responses to currently used anti-SARS-CoV-2 vaccines in PWH on ART. We also outline different strategies that could potentially enhance the vaccine-induced antibody responses in PWH. The review will provide guidance and impetus for further research to improve the immunogenicity of these vaccines in this human population.

Vaccines doi: 10.3390/vaccines12121371

Authors: Bin Ahn Kyu Ri Kang Ye Ji Kim Yoon Kyung Cho Suejung Jo Jae won Yoo Jae Wook Lee Nack-Gyun Chung Bin Cho Dae Chul Jeong Jin Han Kang Hyun Mi Kang

Background: Varicella can lead to severe complications in immunocompromised children, including those undergoing hematopoietic stem cell transplantation (HSCT) or chemotherapy. Preventing primary varicella zoster virus (VZV) infection is crucial in these populations to mitigate morbidity and mortality. This study aimed to evaluate the immunogenicity and safety of the live attenuated MAV/06 varicella vaccine in pediatric patients post-HSCT and post-chemotherapy. Additionally, it sought to compare fluorescent-antibody-to-membrane-antigen (FAMA) and enzyme-linked immunosorbent assay (ELISA) titers to establish effective cut-off levels for protection against varicella. Methods: The FAMA assay was conducted at the Vaccine Bio Research Institute, and a VARICELLA-ZOSTER ELISA (Vircell, Granada, Spain) kit, which relies on lysate from whole cells infected with VZV, was used to determine VZV IgG. A prospective cohort study was conducted with 76 pediatric patients under 18 years old who tested negative for VZV IgG via ELISA. Patients post-HSCT and post-chemotherapy were included. Participants received the MAV/06 varicella vaccine, and serologic responses were evaluated using ELISA and FAMA. Results: The median age of participants was 9.8 years, with acute lymphoid leukemia and acute myeloid leukemia being the most common underlying disease. Post-dose 1, the seropositive rate was 56.1% by ELISA and 97.2% by FAMA. Based on the FAMA seropositive cut-off ≥1:4, post-dose 1 geometric mean titers (GMTs) of seropositive patients in the post-HSCT group were 14.7 (95% CI, 11.3–19.1) versus 20.2 (95% CI, 13.0–31.3) in the post-chemotherapy group (p = 0.690). Based on a FAMA seropositive cut-off ≥1:16, the post-dose 1 GMT of patients considered seropositive in the post-HSCT group was 19.3 (95% CI, 15.6–24.0) versus 34.1 (95% CI, 21.0–55.4) in the post-chemotherapy group (p = 0.116), and post-dose 2 FAMA titers of 76.1 (95% CI, 14.6–398.1) in the post-HSCT group and 64.0 (95% CI, 11.4–358.1) in the post-HSCT group (p = 0.853) were observed. In patients with lower baseline FAMA titers (1:4 to 1:8), 66.7% in the post-HSCT group and 71.5% in the post-chemotherapy group achieved a greater than four-fold increase in FAMA titers post-dose 1, while those with higher baseline titers (≥1:16) did not. There were no serious adverse events or vaccine-related rashes occurring in any of the patients. Conclusion: The MAV/06 varicella vaccine is immunogenic in pediatric patients post-HSCT and post-chemotherapy, particularly when administered in a two-dose schedule using a cut-off FAMA titer of <1:16.

Vaccines doi: 10.3390/vaccines12121370

Authors: Nicole Salisbury Iqbal Hossain Parysa Oskouipour Audry Hong Elan Ebeling Jessica C. Shearer Emily Grapa

Background: Microplanning is widely recognized as a critical tool for improving immunization coverage and equity and is considered a core component of routine immunization. However, there is limited evidence on how microplans are developed and implemented and the effectiveness of microplanning. As such, this study sought to review the existing evidence on implementation and institutionalization of microplanning; identify strategies to improve microplanning; and document evidence on new approaches to microplanning, including digitally enhanced and integrated microplanning. Methods: We employed a three-stage mixed-method approach. First, we conducted a literature review on microplanning for routine immunization. Second, we administered an online survey to gather insights into the factors that constrained and enabled microplanning in low-resource settings. Third, we conducted key informant interviews to better understand the barriers and enablers. Results: We found a paucity of published literature describing the drivers and effectiveness of microplanning and how to sustain it over time. Our review indicates that factors at both the development and implementation stages influence implementation and whether the process is sustained over time. These include the level of community engagement and health care worker ownership, access to data, the complexity of the microplanning tools, and the extent to which supervisors follow up on the plans. Conclusion: Our review indicates that microplanning is successful when health care workers and communities are engaged in the development process. While these findings highlight the benefits of a ‘bottom-up’ approach to microplanning, this may be more resource-intensive, and there remains a need for more research on the costs and benefits.

Vaccines doi: 10.3390/vaccines12121369

Authors: Vachagan Harutyunyan Ann Ottosen Rachel M. Burke Derek Ehrhardt Meredith Shirey Rissa Durham David Woods

Background/Objectives: As we commemorate 50 years of the Expanded Programme on Immunization (EPI), the global mission to eradicate polio stands at a critical juncture. While remarkable progress has been made over the past decades, ensuring a steady supply of polio vaccines remains a significant challenge that could undermine these achievements. This manuscript aims to address the complexities of polio vaccine security within the context of the Immunization Agenda 2030 (IA2030) and the Global Polio Eradication Strategy 2022–2029, proposing actionable strategies to strengthen the vaccine supply. Methods: This manuscript analyzes obstacles to vaccine security, including supply disruptions and market uncertainties. It presents the Polio Vaccine Security Framework as a key strategy for addressing these challenges. Data were gathered from Global Polio Eradication Initiative (GPEI) reports, consultations with key stakeholders, and analyses of past vaccine shortages. Results: The findings indicate that the primary risks to vaccine security include the lack of a coherent long-term policy framework on polio vaccination, the absence of a clear polio vaccine development roadmap, and insufficient long-term, predictable forecasting. Additionally, stronger coordination is needed between stakeholders involved in vaccine supply, polio containment, and research, as well as addressing challenges related to financing and access to resources. Conclusions: A robust, adaptable, and sustainable approach to vaccine security, proposed in the Polio Vaccine Security Framework, is critical to achieving and sustaining polio eradication. Collaboration among policymakers, manufacturers, and stakeholders to implement it is essential to ensure the uninterrupted supply of polio vaccines, protecting the progress made over the past half century, and preventing a resurgence of poliovirus in the future.

Vaccines doi: 10.3390/vaccines12121368

Authors: Yun Kim Ronaldo Iachan John Boyle Yangyang Deng

Background/Objectives: Understanding attitudes and behaviors related to vaccination is critical for enhancing COVID-19 vaccination acceptance and reducing disparities in vaccination coverage. This study examines disparities in vaccine-related attitudes and COVID-19 vaccine hesitancy in the United States in relation to community-level social vulnerability. Methods: This study analyzed cross-sectional national surveys conducted repeatedly between July 2020 and August 2021 (n = 6716). We assessed the association between county-level social vulnerability and general vaccine-related attitudes, as well as COVID-19 vaccine hesitancy. We developed Poisson models with robust variance estimation. The analysis also included the association of county social vulnerability with parental COVID-19 vaccine hesitancy. Results: Living in counties with high Socioeconomic Status vulnerability was associated with less vaccine support (adjusted Prevalence Ratio (aPR) 1.10; 95% CI 1.05–1.14) and residing in counties with high Household Characteristics vulnerability was associated with higher likelihood of COVID-19 vaccine hesitancy (aPR 1.13; 95% CI 1.07–1.20). In contrast, high vulnerability in the Racial and Ethnic Minority was associated with more positive attitudes toward vaccines (aPR 0.91; 95% CI 0.88–0.94) and lower COVID-19 vaccine hesitancy for both themselves (aPR 0.81; 95% CI 0.76–0.87) and children (aPR 0.84; 95% CI 0.75–0.94), after adjusting for sociodemographic factors. Conclusions: Our study highlights the importance of addressing vulnerabilities related to socioeconomic status and household characteristics to reduce disparities in vaccine perceptions and hesitancy in socially vulnerable populations. The findings provide evidence for targeted public health interventions at the community level. They also demonstrate that the relationship between social vulnerability and vaccine attitudes varies across different vulnerability components.

Vaccines doi: 10.3390/vaccines12121367

Authors: Ketty Lysie Libardi Lira Machado Ana Paula Neves Burian Olindo Assis Martins-Filho José Geraldo Mill Lunara Baptista Ferreira Karina Rosemarie Lallemand Tapia Anna Carolina Simões Moulin Isac Ribeiro Moulaz Priscila Dias Cardoso Ribeiro Vanessa de Oliveira Magalhães Erika Biegelmeyer Flávia Maria Matos Melo Campos Peixoto Sandra Lúcia Euzébio Ribeiro Camila Maria Paiva França Telles Juliana Bühring Natalia Sarzi Sartorio Vanessa Hax Rodrigo Poubel Vieira de Rezende Katia Lino Baptista Ana Karla Guedes de Melo Vitor Alves Cruz Rejane Maria Rodrigues de Abreu Vieira Renata Henriques de Azevedo Valderilio Feijó Azevedo Marcelo de Medeiros Pinheiro Odirlei André Monticielo Edgard Torres Dos Reis Neto Andréa Teixeira-Carvalho Ricardo Machado Xavier Emilia Inoue Sato Viviane Angelina de Souza Gilda Aparecida Ferreira Gecilmara Salviato Pileggi Valeria Valim

Background/Objectives: The effectiveness of COVID-19 vaccine in patients with immune-mediated inflammatory diseases (IMID) depends on the underlying disease, immunosuppression degree and the vaccine regimens. We evaluate the safety and immunogenicity of different COVID-19 vaccine schedules. Methods: The SAFER study: “Safety and effectiveness of the COVID-19 Vaccine in Rheumatic Disease”, is a Brazilian multicentric prospective observational phase IV study in the real-life. Data were analyzed after 2 or 3 doses of COVID-19 vaccines: adenoviral vectored vaccine (ChAdOx1 nCoV-19, Astrazeneca), mRNA vaccine (BNT162b2, Pfizer–BioNTech) or inactivated SARS-COV-2 vaccine (CoronaVac, Sinovac Biotech). IgG antibody against SARS-CoV-2 spike (IgG-S) receptor-binding domain level were quantified at baseline (T1) and 28 days after the first (T2), 2nd (T3) and 3rd (T4) doses by chemiluminescence (SARS-CoV-2-IgG-II Quant-assay, Abbott-Laboratories). Results: 721 patients with IMID were included in the analysis. The median titers of IgG-S (BAU/mL) increased progressively over the times: at baseline was 6.26 (5.41–7.24), T2: 73.01 (61.53–86.62), T3: 200.0 (174.36–229.41) and T4: 904.92 (800.49–1022.97). The multivariate linear regression showed that greater IgG-S titers were associated with pre-exposure to COVID-19 (p < 0.001) and BNT162b2 booster vaccine (p < 0.001). Rituximab and immunosuppressant drugs were independent factors for low titers (p = 0.002, p < 0.001, respectively). No serious adverse event was reported. Conclusions: All platforms were safe and induced an increase in IgG-S antibodies. COVID-19 pre-exposure and BNT162b2 booster regimens were predictors of higher humoral immune responses, which is relevant in immunosuppressed populations. Immunosuppressants (mainly rituximab) predicted the lowest antibodies.

Vaccines doi: 10.3390/vaccines12121365

Authors: Yanyan Li Yingying Lin Yunyun Yi Na Zhu Xinyu Cui Xin Li

Objectives: Accumulating evidence has confirmed the efficacy and safety of COVID-19 vaccines against SARS-CoV-2 infection. However, the effect of COVID-19 vaccination on immuno-virological parameters in people with HIV (PWH) is uncertain. Methods: A total of 372 PWH treated at Beijing Ditan Hospital were included. Unvaccinated PWH were matched 1:3 with vaccinated PWH using a propensity score matching algorithm. Differences in immuno-virological markers between the matched groups were analyzed. The Wilcoxon signed rank test was used to test for changes in CD4 and CD8 counts and HIV viral load over two months around vaccination. In addition, we investigated the long-term changes in HIV-related markers in different vaccination dose groups and in the entire vaccinated population. Results: Vaccinated PWH had a higher CD4/CD8 ratio (0.64 (0.49, 0.78) vs. 0.80 (0.56, 1.03), p = 0.037) than unvaccinated PWH within a two-month window after the third dose. There were 337 PWH who received COVID-19 vaccination, and 73.9% (n = 249) received three doses of vaccine. We observed a transient increase in CD4 count and CD4/CD8 ratio within a two-month window after vaccination, especially after the second dose (CD4 count: 583.5 (428.5, 706.8) vs. 618.0 (452.0, 744.0), p = 0.018; CD4/CD8 ratio: 0.70 (0.50, 0.91) vs. 0.71 (0.53, 0.96), p < 0.001)) and the third dose (CD4 count: 575.5 (435.5, 717.0) vs. 577.5 (440.8, 754.8), p = 0.001; CD4/CD8 ratio: 0.70 (0.52, 0.93) vs. 0.79 (0.53, 1.00), p < 0.001)). Recent CD4 counts and CD4/CD8 ratios were lower than after COVID-19 but remained higher than before COVID-19 in vaccinated PWH. In addition, COVID-19 vaccination had no negative effect on HIV viral load. Conclusions: A transient increase in CD4 count and CD4/CD8 ratio was observed after COVID-19 vaccination. However, the enhanced cellular immune response induced by vaccination may diminish over time and return to normal levels. There is no adverse effect of vaccination on HIV viral load.

Vaccines doi: 10.3390/vaccines12121366

Authors: Nina Grasselli Kmet Matej Mavrič Rajko Saletinger

Background: Patients receiving heart transplantation require lifelong immunosuppression and compared to the general population, they have a more than five times higher chance of acquiring COVID-19, and their mortality rates are higher. The aim of the present study was to estimate the epidemiological and clinical characteristics of COVID-19 in heart transplant recipients (HTRs) in Slovenia to estimate the vaccination rate and evaluate possible vaccination-hesitant subgroups. Methods: All SARS-CoV-2-positive HTRs (N = 79) between 1 March 2020 and 31 December 2023 at the Infectious Diseases Department, University Medical Centre Ljubljana, Slovenia, were included retrospectively. Demographic, clinical and vaccination data were extracted from medical documentation and a statistical evaluation was performed. Results: The observed vaccination rate was 63.3%, but among patients who received transplants before the pandemic, it was statistically significantly higher (p = 0.027). Vaccinated HTRs were statistically significantly older (p = 0.004) and had a significantly higher Charlson Comorbidity Index (p = 0.018). Our results indicate no significant differences between vaccinated and unvaccinated HTRs regarding acute respiratory insufficiency (p = 0.135), length of hospital stay (p = 0.106), intensive care unit admission (0.414) and in-hospital mortality (p = 0.317), but we observed statistically more frequently an asymptomatic course in those vaccinated (p = 0.050), and a longer length of stay in vector vaccine recipients (p = 0.011) and in those not re-vaccinated (p = 0.030). There was a significantly higher re-vaccination rate in males (p = 0.005). Conclusions: An asymptomatic course of COVID-19 was more often observed in vaccinated HTRs. Our findings suggest statistically significant differences in COVID-19 vaccine acceptance rates; younger HTRs and those transplanted after the pandemic are more hesitant to vaccinate, while females accept booster doses less frequently.

Vaccines doi: 10.3390/vaccines12121364

Authors: James D. Allen Xiaojian Zhang Jessica M. Medina Matthew H. Thomas Amanda Lynch Ron Nelson Julia Aguirre Ted M. Ross

Background/Objectives: Standard-of-care influenza vaccines contain antigens that are typically derived from components of wild type (WT) influenza viruses. Often, these antigens elicit strain-specific immune responses and are susceptible to mismatch in seasons where antigenic drift is prevalent. Thanks to advances in viral surveillance and sequencing, influenza vaccine antigens can now be optimized using computationally derived methodologies and algorithms to enhance their immunogenicity. Methods: Mice and ferrets that had been previously exposed to historical H1N1 and H3N2 influenza viruses were vaccinated intramuscularly with bivalent mixtures of H1 and H3 recombinant hemagglutinin (rHA) proteins, which were generated using a computationally optimized broadly reactive antigen (COBRA) design methodology. The vaccine antigens were mixed with a cationic lipid nanoparticle adjuvant, Infectimune®, which promotes both humoral and cellular immune responses. Results: Mice and ferrets vaccinated with Infectimune® and COBRA rHAs elicited protective antibody titers against panels of H1N1 and H3N2 influenza viruses isolated over the past 10 years. These animals also had antibodies that neutralized numerous modern H1N1 and H3N2 influenza viruses in vitro. When challenged with the A/Victoria/2570/2019 H1N1 influenza virus, the COBRA rHA vaccinated animals had minimal weight loss, and no detectable virus was present in their respiratory tissues on day 3 post-infection. Conclusions: These results demonstrate that COBRA rHA vaccines formulated with Infectimune® elicit protective antibody responses against influenza strains, which were isolated across periods of time when standard-of-care vaccines were frequently reformulated, thus reducing the need to update vaccines on a nearly annual basis.

Vaccines doi: 10.3390/vaccines12121363

Authors: Ermanno Vitale Veronica Filetti Giorgio Bertolazzi Gabriele Giorgianni Nektaria Zagorianakou Andrea Marino Massimiliano Esposito Vincenzo Restivo Serena Matera Venerando Rapisarda Luigi Cirrincione

Background/Objectives: Tetanus is a serious, non-contagious infection caused by Clostridium tetani, which remains a global health threat despite the availability of an effective vaccine. The current state of immunization for agricultural workers in Italy reveals significant disparities, reflecting a non-homogeneous distribution of vaccination coverage across regions and subgroups. The aim of the study was to investigate the prevalence of tetanus antibodies in a cohort of agricultural workers in Eastern Sicily in order to evaluate possible public health strategies for improving vaccination coverage. Methods: This observational retrospective study assessed tetanus immunization coverage in agricultural workers in Eastern Sicily during the period from 2012–2022. Results: A total of 1143 workers participated, of which 71% (n = 871) had protective tetanus antitoxin levels. Of the 835 vaccinated workers, 9% were not immune, while 19% of those who were not vaccinated or did not recall their vaccination history were immune. Significant gaps in vaccination were noted, particularly among non-European workers, with only 23% vaccinated compared to 89% of European workers. Additionally, vaccination rates were higher in those born after 1963, when vaccination became mandatory. Conclusions: The results underscore the need for targeted vaccination strategies, especially for older and migrant workers, as well as the importance of workplace immunization programs led by occupational physicians. Improving vaccination coverage among agricultural workers is essential for preventing tetanus infections in high-risk agricultural populations.

Vaccines doi: 10.3390/vaccines12121362

Authors: Ekaterina A. Astakhova Konstantin O. Baranov Nadezhda V. Shilova Svetlana M. Polyakova Evgeniy V. Zuev Dmitry A. Poteryaev Alexander V. Taranin Alexander V. Filatov

Background: The COVID-19 pandemic has led to the rapid development of new vaccines and methods of testing vaccine-induced immunity. Despite the extensive research that has been conducted on the level of specific antibodies, less attention has been paid to studying the avidity of these antibodies. The avidity of serum antibodies is associated with a vaccine showing high effectiveness and reflects the process of affinity maturation. In the context of vaccines against SARS-CoV-2, only a limited number of studies have investigated the avidity of antibodies, often solely focusing on the wild-type virus following vaccination. This study provides new insights into the avidity of serum antibodies following adenovirus-based boosters. We focused on the effects of an intranasal Salnavac booster, which is compared, using a single analytical platform, to an intramuscular Sputnik V. Methods: The avidity of RBD-specific IgGs and IgAs was investigated through ELISA using urea and biolayer interferometry. Results: The results demonstrated the similar avidities of serum antibodies, which were induced by both vaccines for six months post-booster. However, an increase in antibody avidity was observed for the wild-type and Delta variants, but not for the BA.4/5 variant. Conclusions: Collectively, our data provide the insights into antibody avidity maturation after the adenovirus-based vaccines against SARS-CoV-2.

Vaccines doi: 10.3390/vaccines12121361

Authors: Emily K. Hendrix Jian Sha Paul B. Kilgore Blake H. Neil Atul K. Verma Ashok K. Chopra

Plague, caused by Yersinia pestis, poses a public health threat not only due to sporadic outbreaks across the globe but also due to its potential as a biothreat agent. Ironically, among the seven deadliest pandemics in global history, three were caused by Y. pestis. Pneumonic plague, the more contagious and severe form of the disease, is difficult to contain, requiring either prophylactic antibiotic treatment or vaccination. However, no vaccine (live attenuated or subunit) is currently approved by the Food and Drug Administration, requiring rigorous preclinical studies in different animal models, thus forming the basis of this study. Objectives: The aim of this study was to evaluate the efficacy and immune responses of two live attenuated vaccines (LAVs), LMA and LMP, either alone or in combination with a trivalent adenoviral vector-based vaccine (Ad5-YFV), in IL-17A-depleted and IgG control mice by using an anti-IL-17A monoclonal antibody (mAb) or its matched isotype IgG, respectively. Methods: IL-17A mAb or IgG isotype control was administered to mice twice per week to their respective groups during the course of immunization. Serum, spleens, and broncho-alveolar lavage fluid (BALF) were collected for assessing immunological responses, and another cohort of mice was intranasally challenged with a lethal dose of parental Y. pestis CO92. Results: Robust humoral and cellular immune responses followed by complete protection were observed in all vaccinated animals against highly lethal intranasal challenge doses of parental Y. pestis CO92. Serum IgG titers to YscF and overall mucosal IgA titers to all three antigens of the Ad5-YFV vaccine were significantly lower, with slightly reduced serum LcrV-neutralizing antibodies when IL-17A was depleted compared to IgG control animals during the course of immunization. A remarkable reduction in Th1 (IFNγ or IL-2) and Th17 cell populations was observed in IL-17A-depleted mice compared to IgG controls in response to vaccination. On the other hand, B cell activities in germinal centers, overall activated antigen-specific T cells, and memory B and T cells remained at comparable levels in both vaccinated IL-17A-depleted and IgG control mice. Conclusions: These data demonstrated the effectiveness of our vaccines even under the reduced levels of both Th1 and Th17 responses and thus should be suitable for those individuals associated with certain immune deficiencies.