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Vaccines, Volume 13, Issue 10 (October 2025) – 75 articles

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12 pages, 2336 KB  
Article
Epidemiological Survey of Porcine Circovirus Type 2 (PCV2) in Large-Scale Pig Farms in Hubei Province and Comprehensive Evaluation of Commercial Vaccine Efficacy
by Wenjun Liao, Zhaofang Xi, Rui Fang, Bang Shen and Junlong Zhao
Vaccines 2025, 13(10), 1066; https://doi.org/10.3390/vaccines13101066 (registering DOI) - 18 Oct 2025
Abstract
Background: Porcine circovirus type 2 (PCV2) is the primary pathogen responsible for postweaning multisystemic wasting syndrome (PMWS) and related diseases, leading to significant economic losses in the global pig industry. Methods: This study conducted a thorough epidemiological survey between 2022 and 2024, gathering [...] Read more.
Background: Porcine circovirus type 2 (PCV2) is the primary pathogen responsible for postweaning multisystemic wasting syndrome (PMWS) and related diseases, leading to significant economic losses in the global pig industry. Methods: This study conducted a thorough epidemiological survey between 2022 and 2024, gathering 6600 samples from 24 large-scale pig farms in Hubei Province. On the basis of these findings, the immune response and economic benefits of two representative commercial PCV2 subunit vaccines, recombinant baculovirus CP08 and Ingelvac CircoFLEX®, were assessed in a modern fattening farm in Xiangyang city. Results: The results indicated no detection of viral antigens in sows; however, weaned piglets and fattening pigs presented high positivity rates, with 8-week-old nursery pigs identified as the peak period for infection. Both vaccines significantly improved average weight gain and reduced antigen positivity, with Ingelvac CircoFLEX® demonstrating superior viral control and economic returns. Conclusions: This study offers valuable scientific and practical guidance for PCV2 control strategies and vaccine selection in Hubei and comparable regions. Full article
(This article belongs to the Section Veterinary Vaccines)
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20 pages, 1181 KB  
Article
The Potential Public Health Impact of the mRNA-Based Respiratory Syncytial Virus Vaccine, mRNA-1345, Under Extended Vaccination Campaigns Among Older Adults in the United Kingdom: A Modelling Study
by Mariia Dronova, Anna Tytuła, Zuzanna Janusz, Parinaz Ghaswalla, Stuart Carroll, Orsolya Balogh and Keya Joshi
Vaccines 2025, 13(10), 1065; https://doi.org/10.3390/vaccines13101065 (registering DOI) - 18 Oct 2025
Abstract
Background/Objectives: Respiratory syncytial virus (RSV) is a leading cause of severe respiratory disease in older adults. Despite growing recognition of RSV as a public health concern, vaccination options remain limited. This study assessed the potential long-term public health impact of extended mRNA-1345 [...] Read more.
Background/Objectives: Respiratory syncytial virus (RSV) is a leading cause of severe respiratory disease in older adults. Despite growing recognition of RSV as a public health concern, vaccination options remain limited. This study assessed the potential long-term public health impact of extended mRNA-1345 RSV vaccination campaigns. Methods: A dynamic transmission model, stratified by age, was developed to evaluate the epidemiological and clinical impact of RSV vaccination in the UK over a 20-year time horizon. Eight vaccination strategies were assessed: two reflecting the JCVI recommendation for the 2024–2025 season and its recent extension, and six extended strategies considering broader eligible age groups, higher coverage, and/or revaccination every 2 or 3 years. Two exploratory analyses and extensive model validation versus reported data were also conducted. Results: Strategies combining broader age eligibility (≥60 years), higher coverage (80%), and 2-year revaccination achieved the greatest impact, preventing 310,000 hospitalisations over 20 years in the total UK population. Exploratory analyses showed that the expected public health impact might exceed the estimates presented in this analysis, if an alternative vaccine efficacy profile or the projected demographic shift would be confirmed. Conclusions: Extended RSV vaccination strategies including broader age eligibility and routine revaccination could offer substantial public health benefits in the UK. Targeting adults aged ≥60 years is expected to be particularly efficient in achieving a sustainable reduction in RSV burden. These findings could provide valuable support for national policy discussions on optimising RSV vaccination strategies in older adults, particularly regarding target age groups, revaccination schedules, and long-term programme planning. Full article
(This article belongs to the Special Issue Respiratory Syncytial Virus (RSV) Vaccine)
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30 pages, 2907 KB  
Systematic Review
Health System Determinants of Delivery and Uptake of HPV Vaccination Services Among Involuntary Migrant Populations: A Qualitative Systematic Review
by Jennifer Nyawira Githaiga, Jill Olivier, Susanne Noll and Edina Amponsah-Dacosta
Vaccines 2025, 13(10), 1064; https://doi.org/10.3390/vaccines13101064 (registering DOI) - 18 Oct 2025
Abstract
Background: Migrant populations are commonly under-immunised relative to general populations in host countries. The evidence base on routine vaccination among migrant children suggests that higher priority is given to infants and younger children compared to adolescents. Though migrants are often classified as a [...] Read more.
Background: Migrant populations are commonly under-immunised relative to general populations in host countries. The evidence base on routine vaccination among migrant children suggests that higher priority is given to infants and younger children compared to adolescents. Though migrants are often classified as a homogenous group, different sub-populations of migrants exist, including voluntary migrants who choose to move and involuntary migrants forcibly displaced by humanitarian crises. The human papillomavirus (HPV) vaccine, a relatively recent addition to global routine immunisation schedules for adolescents, is a useful proxy for understanding vaccine equity for this under-prioritised group. This qualitative systematic review explores health system determinants of delivery and uptake of HPV vaccination services among involuntary migrants. Methods: A literature search was conducted across ten electronic databases. An analytical framework tailored to the migrant context aided in capturing the complexity and magnitude of systemic factors that determine vaccine delivery and uptake among involuntary migrants. Of the 676 records retrieved, 27 studies were included in this review. Results: Key determinants of vaccine delivery include adaptation of immunisation policies for migrant inclusiveness, implementation of migrant-targeted interventions, health provider recommendations, electronic health records, and free vaccines. Uptake determinants include access dependent on legal status, awareness-related determinants akin to culturally appropriate health messaging, and acceptance-related determinants associated with sociocultural beliefs, misinformation, and distrust. Conclusions: Prioritising vaccination programmes linked with non-outbreak-related diseases is challenging in the disruptive context of humanitarian crises given fragile health systems, limited resources, loss of health infrastructure and deployment of health personnel to emergency care. We strongly advocate for global actors at all health systems levels to actively reform national HPV vaccination programmes to enhance inclusivity of adolescent girls in crises settings or resettled in host countries. Full article
(This article belongs to the Special Issue Inequality in Immunization 2025)
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15 pages, 1103 KB  
Article
A Novel Flow Cytometry Array for High Throughput Detection of SARS-CoV-2 Antibodies
by Benyue Zhang, Zhuo Zhang, Yichao Zhao, Jingqiao Lu, Jianmin Fang, Brianne Petritis, Kelly Whittaker, Rani Huang and Ruo-Pan Huang
Vaccines 2025, 13(10), 1063; https://doi.org/10.3390/vaccines13101063 - 17 Oct 2025
Abstract
Background/Objectives: Although the U.S. Food and Drug Administration (FDA) has approved one antiviral treatment and authorized others for emergency use, there is no fully effective antiviral therapy for coronavirus disease 2019 (COVID-19), which is caused by the severe acute respiratory syndrome coronavirus 2 [...] Read more.
Background/Objectives: Although the U.S. Food and Drug Administration (FDA) has approved one antiviral treatment and authorized others for emergency use, there is no fully effective antiviral therapy for coronavirus disease 2019 (COVID-19), which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Assays detecting virus-specific immunoglobulins (Ig) or nucleic acids in large-scale epidemiological, vaccine, and drug development studies remain limited due to high costs, reagent accessibility, and cumbersome protocols. Methods: A multiplex bead-based assay was developed to simultaneously detect human IgM, IgG, and IgA antibodies against the SARS-CoV-2 spike receptor binding domain (RBD) in serum using flow cytometry. Assay performance was evaluated for sensitivity, specificity, reproducibility, and cross-reactivity and compared to another immunoassay platform. Results: The assay enabled simultaneous measurement of three antibody isotypes across 624 samples within 2 h. Intra-plate coefficients of variation (CVs) ranged from 3.16 to 6.71%, and inter-plate CVs ranged from 3.33 to 5.49%, demonstrating high reproducibility. The platform also quantified background noise from nonspecific binding, facilitating straightforward data interpretation. Conclusions: This novel, flexible multiplex bead-based assay utilizing a well-established platform provides a rapid and reproducible approach for detecting SARS-CoV-2-specific antibodies. Its high throughput capacity and low variability make it well suited for large-scale epidemiological, vaccine, and therapeutic studies. The platform’s adaptability further supports application to other infectious diseases, offering an ideal tool for broad immunological surveillance. Full article
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16 pages, 2008 KB  
Article
Optimization of In Vitro Transcription by Design of Experiment to Achieve High Self-Amplifying RNA Integrity
by Chaoying Hu, Haixin Wang, Guanxing Liu, Kelei Li, Xuanxuan Zhang, Lifang Song, Fan Gao, Xing Wu, Qian Wang, Mingchen Liu, Jianyang Liu, Zhihao Fu, Xiao Ma, Miao Xu, Qunying Mao, Zhenglun Liang and Qian He
Vaccines 2025, 13(10), 1062; https://doi.org/10.3390/vaccines13101062 - 17 Oct 2025
Abstract
Background: Self-amplifying mRNA (saRNA) holds promising application prospects. However, due to the inclusion of a replicase sequence, its extended length leads to premature termination during in vitro transcription (IVT), resulting in poor product integrity. This study aims to optimize the IVT process for [...] Read more.
Background: Self-amplifying mRNA (saRNA) holds promising application prospects. However, due to the inclusion of a replicase sequence, its extended length leads to premature termination during in vitro transcription (IVT), resulting in poor product integrity. This study aims to optimize the IVT process for saRNA vaccines to enhance integrity, thereby addressing the key challenge in saRNA vaccine manufacturing. Method: Guided by the Quality by Design (QbD) framework, Design of Experiment (DoE) methodology was employed to design diverse combinations of process parameters for IVT reactions. Predictive models were established to identify critical process parameters (CPPs) influencing integrity and yield. An optimized parameter set and process design space, meeting predefined yield and integrity standards, were developed. The impact of integrity on the immunogenicity of saRNA vaccines was further investigated. Results: Mg2+ concentration exerted the most pronounced effect on saRNA integrity. Under optimized IVT conditions, integrity exceeded 85%. Mathematical modeling simulations defined the IVT design space, meeting the preset criteria of ≥80% integrity and ≥600 μg/100 μL yield while accommodating longer saRNA constructs. Notably, murine model data revealed that higher saRNA integrity significantly enhanced antigen-specific antibody and T-cell responses. Conclusion: This study successfully established a multivariate IVT design space fulfilling preset integrity and yield criteria, providing critical data references for the industrialization and quality specification development of saRNA vaccines. Full article
(This article belongs to the Section Nucleic Acid (DNA and mRNA) Vaccines)
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13 pages, 1515 KB  
Article
Neutralisation of the Immunoglobulin-Cleaving Activity of Streptococcus equi Subspecies equi IdeE by Blood Sera from Ponies Vaccinated with a Multicomponent Protein Vaccine
by Francesco Righetti, Karina Hentrich, Margareta Flock, Sara Frosth, Karin Jacobsson, Joakim Bjerketorp, Anuj Pathak, Noela Ido, Birgitta Henriques-Normark, Lars Frykberg, Romain Paillot, Bengt Guss, Tim Wood, Jan-Ingmar Flock and Andrew Stephen Waller
Vaccines 2025, 13(10), 1061; https://doi.org/10.3390/vaccines13101061 - 17 Oct 2025
Abstract
Background: Streptococcus equi subspecies equi (S. equi) is the cause of strangles, one of the most prevalent diseases of horses worldwide. The disease is characterised by fever and the formation of abscesses in the lymph nodes of the head and [...] Read more.
Background: Streptococcus equi subspecies equi (S. equi) is the cause of strangles, one of the most prevalent diseases of horses worldwide. The disease is characterised by fever and the formation of abscesses in the lymph nodes of the head and neck, which can restrict the airway. A multicomponent subunit vaccine, Strangvac, has been shown to effectively reduce clinical signs of strangles and to reduce its incidence. Objective: The aim of this study was to determine the immune response against the immunoglobulin-cleaving endopeptidase IdeE, a key protective component within the vaccine and the ability of antibodies to neutralize the proteolytic activity of IdeE. Methods: An in vitro assay was developed to measure the functional inhibition of recombinant IdeE by horse sera pre- and post-vaccination. The IdeE-neutralising titres were compared to the corresponding IdeE-specific antibody titres measured by iELISA (indirect Enzyme-Linked Immunosorbent Assay). Results: A significant IdeE-specific antibody response in blood serum collected from ponies was induced after Strangvac vaccinations. Concomitantly, significant increases in the neutralising activity of IdeE occurred, persisting for at least 12 months post-second vaccination. IdeE-neutralising activity was further increased significantly after a third vaccination, even when the third dose was administered 12 months after the second dose, demonstrating that immunological memory to the vaccine persisted for 12 months. There was a significant correlation between the IdeE-neutralising activity of blood sera and the level of IdeE-specific antibodies. Conclusions: These data provide insights into one potential mechanism by which this vaccine protects Equids against or during S. equi infection. Full article
(This article belongs to the Special Issue Animal Diseases: Immune Response and Vaccines)
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34 pages, 2916 KB  
Review
Impediments to Progress Toward Polio Eradication During 2014–2024: Effectively Addressing the Current Challenges
by Steven G. F. Wassilak, Abdinoor Mohamed and John Paul Bigouette
Vaccines 2025, 13(10), 1060; https://doi.org/10.3390/vaccines13101060 - 17 Oct 2025
Abstract
When the Global Polio Eradication Initiative (GPEI) began in 1988, the year 2000 target was clearly ambitious. Nonetheless, among 20 countries with endemic wild poliovirus transmission in 2000, only Afghanistan, Nigeria and Pakistan remained endemic in 2014; successful global eradication was anticipated within [...] Read more.
When the Global Polio Eradication Initiative (GPEI) began in 1988, the year 2000 target was clearly ambitious. Nonetheless, among 20 countries with endemic wild poliovirus transmission in 2000, only Afghanistan, Nigeria and Pakistan remained endemic in 2014; successful global eradication was anticipated within years. Transmission was interrupted in Nigeria after implementing innovative activities; unfortunately, transmission in Afghanistan and Pakistan has continued into 2025. An additional challenge has been controlling outbreaks and interrupting persistent transmission of circulating vaccine-derived poliovirus type 2 detected after global withdrawal of the use of Sabin strain type 2 oral poliovirus vaccine. The impediments to progress since 2014 are detailed and the challenges that the GPEI must successfully mitigate are reviewed herein. Primary challenges since the acute phase of the COVID-19 pandemic include the loss of a sense of urgency and political will/national ownership in stopping poliovirus transmission, lower childhood routine immunization coverage and the decreased quality of outbreak response campaigns. These facets need to be strengthened. Ongoing security challenges require continued vigilance in affected areas of wild poliovirus-endemic countries as well as in countries with persistent transmission of vaccine-derived poliovirus. Eradication can be achieved if the multiple challenges mentioned are urgently and more effectively mitigated. Decreased funding for the GPEI in 2025 represents the primary, acute challenge that, if not urgently addressed, may allow for the reversal of all progress to date. Full article
(This article belongs to the Special Issue Vaccination Strategies for Global Public Health)
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19 pages, 320 KB  
Review
Gender Barriers to Immunization: A Synthesis of UNICEF’s Analyses to Advance Equity and Coverage
by Cristián Mansilla, Alinane Kamlongera and Ibrahim Dadari
Vaccines 2025, 13(10), 1059; https://doi.org/10.3390/vaccines13101059 - 16 Oct 2025
Viewed by 25
Abstract
Background/objectives: Despite global efforts to improve childhood immunization rates, gender-related barriers continue to hinder equitable access to vaccines worldwide. This study synthesizes gender barrier analyses conducted in various countries to better understand these challenges. This evidence synthesis aims to (1) identify the main [...] Read more.
Background/objectives: Despite global efforts to improve childhood immunization rates, gender-related barriers continue to hinder equitable access to vaccines worldwide. This study synthesizes gender barrier analyses conducted in various countries to better understand these challenges. This evidence synthesis aims to (1) identify the main gender-related barriers affecting immunization focusing on zero-dose targets, HPV, and COVID-19 vaccination campaigns; and (2) summarize key recommendations and lessons that have emerged from countries to overcome those gender barriers. Methods: A documentary analysis was used by reviewing data from gender barrier analyses that were conducted by multiple governments with UNICEF support. The study classified barriers using the socio-ecological model (SEM), encompassing systemic, health service, community, household, and individual-level gender barriers. Descriptive statistics and inductive thematic coding were used to analyze data. Results: This synthesis includes 24 documents representing gender barrier analyses across 29 countries. Findings highlight multiple barriers, including systemic discrimination against women in public and healthcare spaces, limited political will to address gender disparities, and limited (sex)-disaggregated and gender data. At the community and household levels, social norms restrict women’s autonomy in seeking immunization services, while household duties (culturally assigned to women) also restrict their access to immunization services. Adolescents face additional challenges, particularly regarding HPV vaccination, due to misconceptions and stigma from families and peers. Conclusions: Addressing gender-related barriers requires a multi-level approach, integrating gender-responsive policies, and comprehensively addressing gender barriers that are hindering the progress of vaccination efforts. UNICEF’s commitment to gender-responsive immunization strategies is critical for achieving the Immunization Agenda 2030 and ensuring equitable vaccine access for all. Full article
(This article belongs to the Special Issue Inequality in Immunization 2025)
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15 pages, 820 KB  
Article
Maternal Cigarette Smoke Exposure Does Not Impair Influenza Vaccine Responsiveness in Murine Offspring
by Ali Dehghani, Johan Garssen, Ingrid van Ark, Gert Folkerts, Jeroen van Bergenhenegouwen and Saskia Braber
Vaccines 2025, 13(10), 1058; https://doi.org/10.3390/vaccines13101058 - 16 Oct 2025
Viewed by 121
Abstract
Background/Objectives: Environmental pollutants can profoundly affect immune development, yet their impact on offspring vaccine responsiveness remains poorly understood. To address this, we investigated the impact of maternal cigarette smoke (CS) exposure, a major contributor to household air pollution, on influenza vaccine responsiveness in [...] Read more.
Background/Objectives: Environmental pollutants can profoundly affect immune development, yet their impact on offspring vaccine responsiveness remains poorly understood. To address this, we investigated the impact of maternal cigarette smoke (CS) exposure, a major contributor to household air pollution, on influenza vaccine responsiveness in offspring. Methods: Pregnant dams were exposed to CS or air during gestation and lactation. Two weeks post-weaning, offspring received two influenza vaccinations. After the booster vaccination, vaccine-specific delayed-type hypersensitivity (DTH), serum immunoglobulins, and splenic T cells were analyzed. Results: Vaccinated offspring exhibited robust DTH responses and comparable levels of vaccine-specific IgG1 and IgG2a, regardless of maternal exposure. Importantly, maternal CS exposure did not affect splenic Th1 cell frequency in vaccinated offspring but increased the frequency of activated Th2 cells. Conclusions: In conclusion, immune development was affected by enhanced Th2 activation, but vaccine efficacy was not impaired. These findings suggest that, under the current conditions of CS exposure (duration, route, and timing) and influenza vaccine dose, vaccine-induced immunity may exhibit resilience even in the presence of environmental immune modulators such as maternal CS exposure. However, these unexpected results highlight the need for further investigation into the broader health implications of maternal pollutant exposure, particularly considering how exposure timing, type, and route, as well as vaccine characteristics, may influence immune development and responsiveness. A deeper understanding of these factors is essential to fully elucidating the clinical relevance of maternal pollutant exposure on childhood vaccine efficacy. Full article
(This article belongs to the Special Issue Effectiveness and Safety of Vaccines in Special Populations)
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16 pages, 10159 KB  
Article
Design and Evaluation of a Broadly Multivalent Adhesins-Based Multi-Epitope Fusion Antigen Vaccine Against Enterotoxigenic Escherichia coli Infection
by Yanyan Jia, Ke Yang, Qijuan Sun, Weiqi Guo, Zhihao Yang, Zihan Duan, Shiqu Zhang, Rongxian Guo, Ke Ding, Chengshui Liao and Shaohui Wang
Vaccines 2025, 13(10), 1057; https://doi.org/10.3390/vaccines13101057 - 16 Oct 2025
Viewed by 54
Abstract
Background: Enterotoxigenic Escherichia coli (ETEC) is a zoonotic pathogen causing diarrhea and mortality in infants and livestock. Its numerous serotypes necessitate the urgent development of multivalent vaccines for effective prevention, thereby reducing public health and economic threats. Methods: Computational bioinformatics analyses [...] Read more.
Background: Enterotoxigenic Escherichia coli (ETEC) is a zoonotic pathogen causing diarrhea and mortality in infants and livestock. Its numerous serotypes necessitate the urgent development of multivalent vaccines for effective prevention, thereby reducing public health and economic threats. Methods: Computational bioinformatics analyses were conducted on five major ETEC adhesins structural subunits (FaeG, FanC, FasA, FimF41a, and FedF). Dominant epitopes were selected and concatenated via flexible linkers, incorporating the PADRE sequence and LTb adjuvant to design a multi-epitope fusion antigen (MEFA). The recombinant MEFA protein was expressed in a prokaryotic system. Furthermore, molecular dynamics simulations, docking, and immune simulations assessed structural stability and immunogenicity. Immunoreactivity was tested by Western blot. Murine immunization evaluated antibody responses, lymphocyte proliferation, cytokine secretion, and protection against ETEC challenge. Results: Structural modeling showed an extended conformation, with docking and simulations indicating strong immune activation. Western blot confirmed MEFA immunoreactivity. MEFA induced high antigen-specific antibody titers, enhanced splenocyte proliferation, and increased IFN-γ and IL-4 secretion, indicating a Th2-biased response in mice. Vaccinated mice survived lethal ETEC challenge and maintained intestinal integrity. Conclusions: The MEFA candidate vaccine effectively induces robust humoral and cellular immune responses and provides protection against ETEC infection, representing a promising strategy for next-generation multivalent ETEC vaccines. Full article
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4 pages, 156 KB  
Correction
Correction: Omole et al. Safety, Tolerability, and Immunogenicity of the Pneumococcal Vaccines PPSV23 or PCV15 Co-Administered with a Booster Dose of mRNA-1273 SARS-CoV-2 Vaccine in Healthy Adults ≥50 Years of Age. Vaccines 2025, 13, 192
by Tosin Omole, Enrique Pelayo, Aaron S. Weinberg, Spyros Chalkias, Zelalem Endale, Gretchen Tamms, Tina M. Sterling, Lori Good, Tulin Shekar, Morgan Johnson, Natalie Banniettis, Ulrike K. Buchwald and Alejandra Esteves-Jaramillo
Vaccines 2025, 13(10), 1056; https://doi.org/10.3390/vaccines13101056 - 16 Oct 2025
Viewed by 104
Abstract
The authors would like to make the following corrections to this published paper [...] Full article
13 pages, 479 KB  
Article
Effect of Influenza Vaccination on Mortality and Heart Failure Hospitalization in Heart Failure Patients
by Chatpetch Maneesopit, Arintaya Phrommintikul, Jackrapong Bruminhent, Ammarin Thakkinstian and Teerapat Yingchoncharoen
Vaccines 2025, 13(10), 1055; https://doi.org/10.3390/vaccines13101055 - 15 Oct 2025
Viewed by 297
Abstract
Background: The association of influenza vaccination and heart failure (HF) hospitalization and mortality in Thai HF patients is unknown. Objective: We wished to investigate associations between receiving an influenza vaccine and all-cause death or HF hospitalization in HF patients. Methods: We retrospectively reviewed [...] Read more.
Background: The association of influenza vaccination and heart failure (HF) hospitalization and mortality in Thai HF patients is unknown. Objective: We wished to investigate associations between receiving an influenza vaccine and all-cause death or HF hospitalization in HF patients. Methods: We retrospectively reviewed medical records from two large tertiary-care centers in Thailand (Ramathibodi Hospital and Maharaj Nakorn Chiang Mai Hospital) with newly diagnosed heart failure between 2013 and 2020 in an outpatient clinic. We examined the relationship between influenza vaccination and outcomes in a propensity-adjusted model. Results: Of 588 patients, 181 (31%) received an influenza vaccination. During a median follow-up of 57 months, influenza vaccination was associated with a 56% reduction in the risk of HF hospitalization or death (HF hospitalization or all-cause death: HR: 0.44; 95% CI: 0.31–0.63; p < 0.001) in an unadjusted analysis. After propensity score adjustment, influenza vaccination, however, was not associated with a reduced risk of all-cause death but was associated with a reduced risk of HF hospitalization (ATE: 3.06 years; 95% CI: 0.14 to 5.98; p = 0.04). Conclusions: In patients with HF, influenza vaccination was not associated with a reduced risk of the composite of all-cause death or HF hospitalization after adjustment for confounders. Full article
(This article belongs to the Section Influenza Virus Vaccines)
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11 pages, 213 KB  
Article
Self-Reporting of Post-Vaccination Symptoms in the COVID-19 Vaccination Process for Teachers in a North Region of Poland
by Tadeusz Jędrzejczyk, Anna Tyrańska-Fobke, Agata Konieczna, Daniel Ślęzak, Monika Waśkow, Katarzyna Brzychcy, Piotr Robakowski and Marlena Robakowska
Vaccines 2025, 13(10), 1054; https://doi.org/10.3390/vaccines13101054 - 14 Oct 2025
Viewed by 248
Abstract
Background: Poland was one of only 10 European countries listed teachers as a priority group for vaccination against COVID-19 among National Vaccination Program (NVP). The aim of this study was to analyse post-vaccination symptoms self-reported by teachers vaccinated under the national COVID-19 vaccination [...] Read more.
Background: Poland was one of only 10 European countries listed teachers as a priority group for vaccination against COVID-19 among National Vaccination Program (NVP). The aim of this study was to analyse post-vaccination symptoms self-reported by teachers vaccinated under the national COVID-19 vaccination programme. Methods: The presented cross-sectional survey was conducted among teachers from all levels of education in public and non-public institutions, who received the SARS-CoV-2 virus vaccination campaign with the vaccine from AstraZeneca as part of the NVP. The survey was conducted using an original, self-designed questionnaire prepared for this study and distributed to teachers in the form of an online survey via email. Bayesian logistic and linear regression were used to estimate the relationship between predictors and dependent variables. Results: A total of 4622 teachers took part in the survey. Of this number, 3908 teachers declared that they had taken the vaccine. (84.5%). In the study group, self-reported late post-vaccination reactions were very strongly [logBF > 3.4] associated with both gender and age. In contrast, self-reporting of serious late post-vaccination symptoms other than fever was very strongly associated only with gender. Only a small proportion of teachers (from 1.45% to 5.34% depending on age and gender) self-reported immediate post-vaccination reaction (up to 15 min after injection). Conclusions: Self-reporting of symptoms is a valuable tool for monitoring the effectiveness and safety of vaccinations and can also contribute to increased satisfaction with the vaccination process, especially when patients are made aware that post-vaccination symptoms are a natural sign of the body’s immune response. Full article
(This article belongs to the Special Issue Safety and Side Effects in SARS-CoV-2 Vaccine)
14 pages, 3692 KB  
Article
B7 Family Molecule VSIG4 Regulates Pulmonary Anti-Influenza Immune Responses via C-Type Lectin Signal Pathway
by Jianxin Zhu, Dan Lu, Liangyan Zhang, Zhili He, Tianxinyu Ma, Yakun Sun, Wenjing Yu, Xiaolan Yang, Yeqing Tu, Yitai Fang, Deyu Li, Rui Zheng, Tao Li, Jin Zhao and Hui Wang
Vaccines 2025, 13(10), 1053; https://doi.org/10.3390/vaccines13101053 - 14 Oct 2025
Viewed by 421
Abstract
Background: As the member of the B7 family, V-set and immunoglobulin domain-containing 4 (VSIG4) plays an essential role in regulating immune responses against bacterial infection, autoimmune disease, and chronic viral infection. However, the role of VSIG4 in acute viral infections remains largely [...] Read more.
Background: As the member of the B7 family, V-set and immunoglobulin domain-containing 4 (VSIG4) plays an essential role in regulating immune responses against bacterial infection, autoimmune disease, and chronic viral infection. However, the role of VSIG4 in acute viral infections remains largely unclear. Methods: Here, we constructed a gene-targeted VSIG4-deficient mouse model and then infected it with influenza to explore the detailed VSIG4-involved mechanism. Results: Our results demonstrated that the gene-deficient mice exhibited reduced survival rates, ranging from 25% to 50%, after being infected with different influenza virus strains. At the sites of infection, an increased number of CD8+ T cells, along with heightened expression of pro-inflammatory cytokines, e.g., Il-6 and TNFα, may have contributed to tissue damage. The recombinant VSIG4 protein slightly improved protection from the influenza challenge, suggesting regulatory functions of VSIG4 during infection. Using in vitro cell models, we show that the type C lectin receptor pathway member DC-SIGNR1 (CD209) is an essential factor during acute virus infection. The affinity and CO-IP tests indicated an interaction between CD209 and VSIG4, but not through protein modification. Conclusions: Therefore, VSIG4 functionally protected mice by regulating the type C lectin receptor pathway to inhibit excessive Th1 immune responses and inflammation. Our findings highlight the importance of considering immune homeostasis in the development of therapies for severe infections. Full article
(This article belongs to the Section Pathogens-Host Immune Boundaries)
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19 pages, 5486 KB  
Article
Establishment of Immune Biobank for Vaccine Immunogenicity Prediction Using In Vitro and In Silico Methods Against Porcine Reproductive and Respiratory Syndrome Virus
by Chaitawat Sirisereewan, John J. Byrne, Lanre Sulaiman, Abigail Williams, Ben M. Hause, Juliana Bonin Ferreira, Glen W. Almond, Benjamin Gabriel, Anne S. De Groot, Tobias Käser, Gustavo Machado and Elisa Crisci
Vaccines 2025, 13(10), 1052; https://doi.org/10.3390/vaccines13101052 - 14 Oct 2025
Viewed by 472
Abstract
Background/Objectives: Porcine reproductive and respiratory syndrome virus (PRRSV) remains one of the most economically significant pathogens in the global swine industry. Despite the availability of commercial vaccines for over three decades, they fail to induce sterile immunity and often provide inconsistent protection against [...] Read more.
Background/Objectives: Porcine reproductive and respiratory syndrome virus (PRRSV) remains one of the most economically significant pathogens in the global swine industry. Despite the availability of commercial vaccines for over three decades, they fail to induce sterile immunity and often provide inconsistent protection against heterologous PRRSV strains. This study aimed to predict vaccine immunogenicity by detecting strain-specific immune responses that related to an immune correlate of protection (CoP) against different PRRSV-2 strains. Methods: Post-weaning pigs were vaccinated with five commercially available PRRSV-2 vaccines or received sterile PBS injection as a control. At 28 days post-vaccination (dpv), all pigs were humanely euthanized for large-volume blood collection to isolate peripheral blood mononuclear cells (PBMCs) and plasma, establishing the immune bank. PBMCs and plasma from each group were then tested against six PRRSV-2 strains to evaluate immune responses. In addition, T cell epitope coverage between vaccine and field PRRSV-2 strains was assessed using the EpiCC (in silico) tool to enhance predictive capacity. Results: While neutralizing antibodies were undetectable in all vaccinated pigs at 28 dpv, PRRSV-specific IFNγ–producing cells were detected at various levels in each vaccinated group following restimulation with different PRRSV-2 strains. Additionally, a positive correlation was observed for the EpiCC coverage of the N gene and mean IFNγ responses to VR2332 (SLA class I and II) and NC24-6 (SLA class II). Conclusions: The PRRSV immune bank demonstrated potential as a tool for predicting vaccine immunogenicity against different PRRSV-2 strains and EpiCC provides additional information on T cell epitope cross conservation. The combined approach may provide a valuable framework for selecting PRRSV vaccines for more effective prevention and control in endemic areas. Full article
(This article belongs to the Special Issue Animal Vaccines: 2nd Edition)
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17 pages, 444 KB  
Article
Boosting RSV Immunization Uptake in The Netherlands: (Expectant) Mothers and Healthcare Professionals’ Insights on Different Strategies
by Lisanne van Leeuwen, Lisette Harteveld, Lucy Smit, Karlijn Vollebregt, Debby Bogaert and Marlies van Houten
Vaccines 2025, 13(10), 1051; https://doi.org/10.3390/vaccines13101051 - 14 Oct 2025
Viewed by 324
Abstract
Background: Respiratory syncytial virus (RSV) is a major cause of infant respiratory illness, leading to significant hospitalizations. Two preventive strategies exist: maternal vaccination and a long-acting monoclonal antibody for neonates. In The Netherlands, neonatal immunization is planned to start from autumn 2025 onward, [...] Read more.
Background: Respiratory syncytial virus (RSV) is a major cause of infant respiratory illness, leading to significant hospitalizations. Two preventive strategies exist: maternal vaccination and a long-acting monoclonal antibody for neonates. In The Netherlands, neonatal immunization is planned to start from autumn 2025 onward, contingent on acceptance by parents and healthcare professionals. Maternal vaccination is already available at own costs. Understanding acceptance, perceptions, and barriers is critical for effective implementation. This study explores these factors to inform strategies for optimal uptake. Methods: This mixed-method study involved semi-structured online interviews with 21 (expectant) mothers (EMs) and 32 healthcare professionals (HCPs) involved in maternal and neonatal care (e.g., pediatricians, youth doctors/nurses, obstetricians, midwives, and general practitioners) and a quantitative descriptive analysis of factors influencing EM choices. Interviews were transcribed and thematically analyzed. Results: Both EMs and HCPs showed strong support for RSV immunization, with a preference for maternal vaccination or a combined approach. Concerns about neonatal injections during the sensitive postpartum period and unfamiliarity with newborn injections (e.g., vitamin K) influenced preferences. EMs noted hesitation about additional pregnancy/postpartum vaccinations, emphasizing the importance of well-timed interventions. HCPs highlighted logistical challenges, such as defining responsibilities, navigating National Immunization Program (NIP) changes, and ensuring readiness. All interviewed individuals value the option to choose between strategies, necessitating informed decision-making and respect for preferences. EMs make their final decision together with their partner, supported by expert information and their personal environment. Conclusions: Support for RSV immunization is high, with maternal vaccination preferred, though neonatal immunization is accepted if appropriately timed. Providing clear personalized and consistent information, heightened public awareness of RSV’s impact, respecting individual choices, and offering options are key to maximizing uptake. Full article
(This article belongs to the Special Issue Vaccination Strategies for Global Public Health)
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16 pages, 1001 KB  
Article
Prevalence of High-Risk Human Papillomaviruses (HPV) in Slovenian Women Attending Organized National Cervical Cancer Screening 14 Years After Implementation of the National HPV Vaccination Program
by Mateja Lasič, Anja Oštrbenk, Špela Smrkolj, Klara B. Bohinc, Ana Pflaum and Mario Poljak
Vaccines 2025, 13(10), 1050; https://doi.org/10.3390/vaccines13101050 - 13 Oct 2025
Viewed by 601
Abstract
Background/Objectives: To assess overall and type-specific HPV vaccine effectiveness in central and eastern Europe (CEE), the age-stratified prevalence of cervical HPV infection was determined among Slovenian women aged 20 to 64 attending a cervical cancer screening program 14 years after implementation of [...] Read more.
Background/Objectives: To assess overall and type-specific HPV vaccine effectiveness in central and eastern Europe (CEE), the age-stratified prevalence of cervical HPV infection was determined among Slovenian women aged 20 to 64 attending a cervical cancer screening program 14 years after implementation of a national HPV vaccination program, which was then compared with 2009–2010 pre-vaccination data using the same methodological approach. Methods: Cervical samples of 4419 women were tested in 2023–2025 using the clinically validated Alinity m HR HPV Assay, and individual HPV types were determined by the Allplex HPV HR Detection assay. Results were compared with 2009–2010 pre-vaccination data generated using the same assay on an age-range matched cohort of women. Results: The overall prevalence of the 14 Alinity-targeted HPV types was 10.0% in 2023–2025 versus 13.3% in 2009–2010 (p < 0.001). HPV16 prevalence declined from 3.5% to 1.5% (p < 0.001), and HPV18 prevalence from 1.1% to 0.5% (p = 0.005). In women aged 20 to 24 with 40% uptake of quadrivalent HPV vaccine, overall HPV prevalence dropped from 25.3% to 12.8% (p < 0.001). No single case of HPV16/HPV18 infection was detected among vaccinated women. Conclusions: The first large-scale, systematic, and methodologically consistent study of HPV vaccine effectiveness in CEE showed a substantial reduction in high-risk HPV prevalence after implementation of the national program, with the greatest decline among women aged 20 to 24, who harbored the highest HPV burden in the pre-vaccination era. These locally acquired data will considerably inform public health strategies on cervical cancer elimination in CEE. Full article
(This article belongs to the Special Issue HPV Vaccination and Primary HPV Screening)
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1 pages, 122 KB  
Correction
Correction: Castro et al. Stakeholders’ Understanding of European Medicine Agency’s COVID-19 Vaccine Information Materials in EU and Regional Contexts. Vaccines 2023, 11, 1616
by Indiana Castro, Marie Van Tricht, Nicole Bonaccorso, Martina Sciortino, Juan Garcia Burgos, Claudio Costantino and Rosa Gonzalez-Quevedo
Vaccines 2025, 13(10), 1049; https://doi.org/10.3390/vaccines13101049 - 13 Oct 2025
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Abstract
The author would like to make the following correction to this publication [...] Full article
17 pages, 2409 KB  
Article
Immunogenicity and Contraceptive Potential of a Classical Swine Fever Viral Vector Live Vaccine Strain Containing Pig Gonadotropin-Releasing Hormone
by Dong-Jun An, Ji-Hee Shin, SeEun Choe, Young-Hyeon Lee, Min-Kyung Jang, Byung-Hyun An, Gyu-Nam Park, Yun-Sang Cho and Kyung-Soo Chang
Vaccines 2025, 13(10), 1048; https://doi.org/10.3390/vaccines13101048 - 12 Oct 2025
Viewed by 579
Abstract
Background: Classical swine fever virus (CSFV) is a highly contagious and fatal disease in pigs and wild boars. While hunting and bait vaccination are effective for CSFV eradication, additional strategies are needed to control wild boar populations. This study aimed to develop an [...] Read more.
Background: Classical swine fever virus (CSFV) is a highly contagious and fatal disease in pigs and wild boars. While hunting and bait vaccination are effective for CSFV eradication, additional strategies are needed to control wild boar populations. This study aimed to develop an oral vaccine, Flc-LOM-GnRHx3, by inserting gonadotropin-releasing hormone (GnRH) epitopes into the Flc-LOM clone. Methods: The Flc-LOM-GnRHx3 strain was rescued from CPK cells and propagated to high titers in MDBK cells. Male boars (20 weeks old) received three doses (105.0 TCID50/ml/dose) of Flc-LOM-GnRHx3 either orally or intramuscularly at 2-week intervals. Anti-CSFV E2 antibodies were detected via immunofluorescence and Western blotting. Results: Both vaccination routes induced anti-GnRH antibodies and reduced testosterone levels. Testis size and weight were slightly lower than controls, with seminiferous tubule and spermatid deformities observed in 52.5% of intramuscularly vaccinated pigs and 20.8% of orally vaccinated pigs. Conclusions: Flc-LOM-GnRHx3 demonstrates potential as a dual-function oral vaccine that can eradicate CSFV and impair reproductive capacity in wild boars, offering a novel approach for integrated disease control and population management. Full article
(This article belongs to the Special Issue Classical Swine Fever Virus Vaccines)
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15 pages, 1430 KB  
Article
Precautionary Health Behaviours as Potential Confounders in COVID-19 Vaccine Effectiveness Studies
by Chloé Wyndham-Thomas, Leonie de Munter, Kok Yew Ngew, Sanskruti Gaikwad, Konstantina Chatzikonstantinidou, Antonio Carmona, Charlotte Martin, Gerrit Luit ten Kate, Nicolas Praet, Wilhelmine Meeraus, Matthew D. Rousculp and Kaatje Bollaerts
Vaccines 2025, 13(10), 1047; https://doi.org/10.3390/vaccines13101047 - 12 Oct 2025
Viewed by 532
Abstract
Background/Objectives: Precautionary health behaviours (PHBs), such as hand-washing or self-isolation, are non-pharmaceutical interventions used to reduce SARS-CoV-2 transmission. We investigated the potential confounding by PHBs of COVID-19 vaccine effectiveness (VE) estimates in a subset of study participants enrolled in id.DRIVE. Methods: [...] Read more.
Background/Objectives: Precautionary health behaviours (PHBs), such as hand-washing or self-isolation, are non-pharmaceutical interventions used to reduce SARS-CoV-2 transmission. We investigated the potential confounding by PHBs of COVID-19 vaccine effectiveness (VE) estimates in a subset of study participants enrolled in id.DRIVE. Methods: The id.DRIVE COVID-19 VE study (formerly COVIDRIVE) is a European multicentre test-negative case–control study estimating COVID-19 VE against hospitalisation due to laboratory-confirmed SARS-CoV-2 in patients with severe acute respiratory infection. All adults (≥18 y) prospectively enrolled between 16 November 2021 and 16 August 2023 at three sites were invited to complete a PHB survey capturing indicators of PHBs in the 3 months preceding admission. Fisher’s exact test with Bonferroni-adjusted threshold was used to measure the level of association between PHB indicators and both COVID-19 vaccine status and SARS-CoV-2 test result. VE estimates were generated with and without adjustment for PHBs. Results: PHBs were modified over time, with higher precautionary attitudes in the first COVID-19 vaccine booster season (2021–2022) compared to the second one (2022–2023). For the first booster season, PHBs were positively associated with exposures (vaccination status) and outcomes (case or control status). Adjusting for PHBs led to a 6 to 9 percentage-point increase in VE estimates. Conversely, no confounding by PHBs was observed in the second booster season. Conclusions: PHBs should be considered a possible confounder of COVID-19 VE studies. Further research is needed to define when PHBs should be integrated into VE models, as the level of confounding may differ according to the study population and the epidemiological context. Full article
(This article belongs to the Special Issue Advance Public Health Through Vaccination)
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15 pages, 852 KB  
Article
Effect of Influenza Vaccination on the Disease Severity and Viral Load Among Adult Outpatients and Inpatients
by Alexander Domnich, Vincenzo Paolozzi, Giada Garzillo, Andrea Orsi and Giancarlo Icardi
Vaccines 2025, 13(10), 1046; https://doi.org/10.3390/vaccines13101046 - 10 Oct 2025
Viewed by 698
Abstract
Background: Some studies suggest that, thanks to the mechanisms of immune-mediated attenuation, influenza vaccination reduces severity of influenza illness in breakthrough infections. This study aimed to assess whether influenza vaccination attenuates severity of laboratory-confirmed influenza among Italian adults. Methods: This secondary [...] Read more.
Background: Some studies suggest that, thanks to the mechanisms of immune-mediated attenuation, influenza vaccination reduces severity of influenza illness in breakthrough infections. This study aimed to assess whether influenza vaccination attenuates severity of laboratory-confirmed influenza among Italian adults. Methods: This secondary analysis included all influenza cases detected during respiratory surveillance studies conducted in outpatient and inpatient settings in Genoa (Italy), throughout the 2023/2024 and 2024/2025 seasons. Here, we compared viral load and the count of influenza-related symptoms in outpatients, alongside all-cause in-hospital mortality and radiologically confirmed pneumonia in inpatients, between vaccinated and unvaccinated adults. Results: The study included 188 influenza cases diagnosed in primary care and 281 influenza cases identified among inpatients. Of these, 37.2% and 31.7%, respectively, were vaccinated, constituting breakthrough infections. Compared to unvaccinated adults, vaccinated outpatients had a slightly lower viral load (difference in cycle threshold values of 1.36 corresponding to about 0.51 log10 reduction in the number of copies/mL; p = 0.077), primarily driven by influenza A(H1N1)pdm09. Vaccinated outpatients also reported 9% fewer influenza-related symptoms than unvaccinated counterparts [prevalence ratio 0.91; 95% confidence interval (CI): 0.84, 0.99]. Among hospitalized older adults, influenza vaccination was associated with 64% reduced odds of in-hospital death (odds ratio 0.36; 95% CI: 0.12, 0.94). Conversely, no association between vaccination and development of pneumonia was found. Conclusions: This study corroborates the idea that influenza vaccination attenuates disease severity in breakthrough infections. These effects are, however, dependent on the measure of severity used. Full article
(This article belongs to the Special Issue The Effectiveness of Influenza Vaccine)
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18 pages, 319 KB  
Review
Health Technology Assessment of mRNA Vaccines: Clinical, Economic, and Public Health Implications
by Giovanni Genovese, Caterina Elisabetta Rizzo and Cristina Genovese
Vaccines 2025, 13(10), 1045; https://doi.org/10.3390/vaccines13101045 - 10 Oct 2025
Viewed by 687
Abstract
Health Technology Assessment (HTA) is a multidimensional and multidisciplinary approach for analyzing the medical–clinical, social, organizational, economic, ethical, and legal implications of a technology, through the evaluation of multiple dimensions such as efficacy, safety, costs, and social–organizational impact. In the healthcare context, “technology” [...] Read more.
Health Technology Assessment (HTA) is a multidimensional and multidisciplinary approach for analyzing the medical–clinical, social, organizational, economic, ethical, and legal implications of a technology, through the evaluation of multiple dimensions such as efficacy, safety, costs, and social–organizational impact. In the healthcare context, “technology” refers to any tool—including pharmaceuticals (or, in this case, vaccines)—that is applied to healthcare practice. HTA focuses on assessing both the real and potential effects of a given technology, either prospectively or throughout its life cycle, as well as the consequences that the introduction or exclusion of an intervention may have on the healthcare system, the economy, and society at large. Full article
12 pages, 852 KB  
Perspective
Advancing Inequality Monitoring in Immunization: Reflecting on 10 Years of WHO Contributions
by Nicole Bergen, Katherine Kirkby, Anne Schlotheuber and Ahmad Reza Hosseinpoor
Vaccines 2025, 13(10), 1044; https://doi.org/10.3390/vaccines13101044 - 10 Oct 2025
Viewed by 490
Abstract
Major immunization programs and initiatives have prioritized the advancement of equity in immunization. Over the past decade, the World Health Organization has made contributions to understanding inequalities in immunization, including global analyses of immunization inequality as well as tools for knowledge dissemination and [...] Read more.
Major immunization programs and initiatives have prioritized the advancement of equity in immunization. Over the past decade, the World Health Organization has made contributions to understanding inequalities in immunization, including global analyses of immunization inequality as well as tools for knowledge dissemination and capacity strengthening. This article provides an overview of these contributions, highlighting key findings of scholarly reports and journal articles and identifying areas for further research and development to expand monitoring efforts and enhance their impact. Global analyses have primarily drawn from household survey data to explore inequalities related to economic status, education, gender, and geography. Reports and articles address childhood immunization, COVID-19 vaccine indicators, and maternal tetanus protection. Inequalities were reported across all dimensions, with variation by country and income grouping. Time trends generally suggest persistent, though narrowing, inequalities. Areas for further development include the following: increasing awareness and political support for advancing equity in immunization; expanding the collection, availability, and use of disaggregated immunization data; continuous capacity building of inequality monitoring, especially at national and subnational levels; adapting inequality monitoring practices to changing contexts and priorities; strengthening the links between data/evidence and action/impact; and building on existing partnerships and collaborations. Full article
(This article belongs to the Special Issue Inequality in Immunization 2025)
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5 pages, 150 KB  
Editorial
Biotechnology and the Future of Vaccines—From Novel Routes and Vectors to Safety, Efficacy, and Global Impact
by Tsu-Hsiang Kuo and Yuan-Chuan Chen
Vaccines 2025, 13(10), 1043; https://doi.org/10.3390/vaccines13101043 - 10 Oct 2025
Viewed by 486
Abstract
Vaccines remain one of the greatest achievements in biomedical science, credited with the eradication of smallpox, the near-elimination of polio and the prevention of many deaths from infectious diseases [...] Full article
(This article belongs to the Special Issue Biotechnologies Applied in Vaccine Research)
14 pages, 1305 KB  
Article
Serological Response to COVID-19 Vaccination in Saudi Arabia: A Comparative Study of IgG and Neutralising Antibodies Across Vaccine Platforms
by Mariam M. AlEissa, Ahdab A. Alsaieedi, Reema Alduaiji, Fahad Almsned, Yousif AlDossary, Nada Saleh, Raghad A. AlQurashi, Esraa A. Hawsa, Muath b Ben Shaded, Amer M. Alshehri, Osamah T. Khojah, Eyad Y. Abu Sarhan, Hamad H. Alonazi, Walid A. Nouh, Khalid H. AlAnazi, Sami S. Almudrra, Khaled I. AlAbdulkareem, Abdullah AlJurayyan and Abdullah M. Asiri
Vaccines 2025, 13(10), 1042; https://doi.org/10.3390/vaccines13101042 - 10 Oct 2025
Viewed by 774
Abstract
Background: In the Kingdom of Saudi Arabia, various COVID-19 vaccines were administered during the pandemic. However, region-specific real-word comparative data on their immunogenicity remain limited. This study aimed to assess the serological responses to Pfizer-BioNTech (BNT162b2), Moderna (mRNA-1273), and AstraZeneca (ChAdOx1 nCoV-19) [...] Read more.
Background: In the Kingdom of Saudi Arabia, various COVID-19 vaccines were administered during the pandemic. However, region-specific real-word comparative data on their immunogenicity remain limited. This study aimed to assess the serological responses to Pfizer-BioNTech (BNT162b2), Moderna (mRNA-1273), and AstraZeneca (ChAdOx1 nCoV-19) vaccines in a diverse population living in KSA. Methods: This observational study included 236 adults recruited from vaccination sites in Riyadh. Participants provided serum samples at predefined intervals: before the first dose, after the first dose, after the second dose, and post-vaccination infection (if applicable). IgG and neutralising antibodies were quantified using ELISA assays. Demographic and vaccination data, and their associations with antibody responses, were evaluated. Results: At baseline, 75.4% of participants were positive for SARS-CoV-2 IgG, suggesting high prior exposure. Marked incremental increases in IgG levels were observed after each vaccine dose. Both Moderna and Pfizer elicited stronger responses, with Pfizer inducing the strongest early response and Moderna achieving the highest overall titres. Among IgG-positive individuals, neutralising antibodies were detected in 98.1%. There were no statistically significant differences by age or gender, although males tended to show higher mean titres. Heterologous vaccine schedules induced comparable or enhanced immunogenicity relative to homologous schedules, supporting their use in flexible immunisation strategies. Conclusions: All COVID-19 vaccines administered in Saudi Arabia elicited robust antibody responses, particularly the mRNA-based vaccines. Our findings support their continued use and justify varied vaccination approaches, including mix-and-match booster strategies, to enhance community immunity. Full article
(This article belongs to the Section COVID-19 Vaccines and Vaccination)
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22 pages, 1862 KB  
Article
Production of Clinical-Grade SARS-CoV-2 Spike Ferritin Nanoparticle Protein Immunogen by Transient Transfection
by Agnes Hajduczki, William C. Chang, Rafael De La Barrera, James F. Wood, Wei-Hung Chen, Elizabeth J. Martinez, Jaime L. Jensen, Rajeshwer S. Sankhala, Clayton Smith, Alexander Anderson, Elaine B. Morrison, Caroline E. Peterson, Phyllis A. Rees, Sandrine Soman, Caitlin Kuklis, Aslaa Ahmed, Jocelyn King, Farooq Nasar, Courtney Corbitt, Misook Choe, Paul V. Thomas, Michelle Zemil, Lindsay Wieczorek, Victoria R. Polonis, Helen M. Dooley, John R. Mascola, Natalie de Val, Gary R. Matyas, Mangala Rao, Gregory D. Gromowski, Kayvon Modjarrad, Sandhya Vasan, Jeffrey W. Froude, Nelson L. Michael, M. Gordon Joyce and Stasya Zarlingadd Show full author list remove Hide full author list
Vaccines 2025, 13(10), 1041; https://doi.org/10.3390/vaccines13101041 - 9 Oct 2025
Viewed by 406
Abstract
Background/Objectives: In response to the COVID-19 pandemic, we developed a vaccine candidate against SARS-CoV-2. Spike Ferritin Nanoparticle (SpFN) comprises 24 identical prefusion-stabilized spike proteins anchored to a self-assembled nanoparticle. Organized along the three-fold axis of the ferritin particle, eight SARS-CoV-2 spike trimers [...] Read more.
Background/Objectives: In response to the COVID-19 pandemic, we developed a vaccine candidate against SARS-CoV-2. Spike Ferritin Nanoparticle (SpFN) comprises 24 identical prefusion-stabilized spike proteins anchored to a self-assembled nanoparticle. Organized along the three-fold axis of the ferritin particle, eight SARS-CoV-2 spike trimers are presented per nanoparticle. Methods: Here, we describe the CGMP processes for manufacturing SpFN using transient transfection of Expi293F cells. Results: The final yield of SpFN was ~10 mg per liter of media supernatant. The resulting protein is stable in cold storage for two years at −20 °C, as well as for a month at room temperature, and can withstand multiple freeze/thaw cycles. SpFN material produced using the CGMP protocols adjuvanted with Army Liposomal Formulation-QS-21 (ALFQ) elicited potent neutralizing antibodies against WA-1, Alpha, Beta, and Delta variants in mice as measured by a pseudovirus neutralization assay. Conclusions: This work demonstrates rapid development and scaled-up production of clinical-grade SARS-CoV-2 vaccine protein material, allowing permissive storage and transport conditions, and serves as a framework for recombinant protein production for future emergent pathogens. Full article
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28 pages, 1351 KB  
Article
Strengthening Primary Health Care Through Implementation Research: Strategies for Reaching Zero-Dose Children in Low- and Middle-Income Countries’ Immunization Programs
by Boniface Oyugi, Karin Kallander and A. S. M. Shahabuddin
Vaccines 2025, 13(10), 1040; https://doi.org/10.3390/vaccines13101040 - 9 Oct 2025
Viewed by 685
Abstract
Introduction: Despite global improvements in immunization, major gaps persist. By 2024, an estimated 14.3 million infants, predominantly in low- and middle-income countries (LMICs), remained zero-dose (ZD), never having received even the first DTP vaccine. In 2022, 33 million children missed their measles vaccination [...] Read more.
Introduction: Despite global improvements in immunization, major gaps persist. By 2024, an estimated 14.3 million infants, predominantly in low- and middle-income countries (LMICs), remained zero-dose (ZD), never having received even the first DTP vaccine. In 2022, 33 million children missed their measles vaccination (22 million missed the first dose, 11 million missed the second dose), highlighting entrenched structural, behavioral, and systemic barriers that continue to exclude marginalized populations. Addressing these inequities requires innovative, context-adapted approaches that strengthen primary health care (PHC) and extend services to the hardest-to-reach populations. Objectives: This study aims to document and synthesize implementation research (IR) projects on immunization programs in LMICs, identifying key enablers and effective strategies that reduce inequities, improve outcomes, and support efforts to reach ZD children. Methods: We conducted a retrospective multiple-case study of 36 IR projects across 13 LMICs, embedded within an evidence review framework and complemented by policy analysis. Data were drawn from systematic document reviews and validation discussions with project leads. A total of 326 strategies were extracted, coded using a structured codebook, and mapped to the WHO–UNICEF PHC Levers for Action. Descriptive analysis synthesized patterns across service delivery and policy outcomes, including coverage gains, improved microplanning, community engagement, and system integration. Results: Of the 326 immunization strategies identified, most (76.1%) aligned with operational PHC levers, particularly monitoring and evaluation (19.3%), workforce development (18.7%), and models of care (12%). Digital technologies (11.7%) were increasingly deployed for real-time tracking and oversight. Core strategic levers comprised 23.9% of strategies, with community engagement (8.9%) and governance frameworks (7.7%) emerging as critical enablers, though sustainable financing (4%) and private-sector engagement (0.9%) were rarely addressed. While the majority of projects focused on routine immunization (n = 32), only a few directly targeted ZD children (n = 3). Interventions yielded improvements in both service delivery and policy outcomes. Improvements in microplanning and data systems (23.5%) reflected the increased uptake of digital dashboards, GIS-enabled tools, and electronic registries. Community engagement (16.2%) emphasized the influence of local leaders and volunteers in building trust, while health system strengthening (15.7%) invested in cold chain, supervision, and workforce capacity. Coverage gains (10.6%) were achieved through delivery innovations, though sustainable financing remained a critical problem (3.4%). Conclusions: Reaching ZD children requires equity-driven strategies that combine digital innovations, community engagement, and resilient system planning. Sustained progress depends on strengthening governance, financing, and research. Embedding IR in immunization programs generates actionable evidence, supports context-specific strategies, and reduces equity gaps, offering practical insights that complement health system research and advance the Immunization Agenda 2030. Full article
(This article belongs to the Special Issue Inequality in Immunization 2025)
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20 pages, 2984 KB  
Article
A Single Dose of Live-Attenuated Rift Valley Fever Virus Vector Expressing Peste Des Petits Ruminants Virus (PPRV) H or F Antigens Induces Immunity in Sheep
by Sandra Moreno, Gema Lorenzo, Verónica Martín, Celia Alonso, Friedemann Weber, Belén Borrego and Alejandro Brun
Vaccines 2025, 13(10), 1039; https://doi.org/10.3390/vaccines13101039 - 9 Oct 2025
Viewed by 493
Abstract
Introduction/Background: Rift Valley fever virus (RVFV) and peste des petits ruminants virus (PPRV) are significant pathogens affecting small ruminants, causing substantial economic losses in the affected regions. The development of effective vaccines against both viruses is crucial for disease control. Recombinant viruses expressing [...] Read more.
Introduction/Background: Rift Valley fever virus (RVFV) and peste des petits ruminants virus (PPRV) are significant pathogens affecting small ruminants, causing substantial economic losses in the affected regions. The development of effective vaccines against both viruses is crucial for disease control. Recombinant viruses expressing heterologous antigens have shown promise as multivalent vaccine candidates. Unlike conventional PPRV vaccines, our recombinant RVFV-vectored vaccines offer a novel dual-protection strategy against RVF and PPR, combining safety, immunogenicity, and a DIVA strategy. Methods: Recombinant RVFVs (ZH548 strain) were generated to express either the hemagglutinin (H) or fusion (F) proteins from the PPRV strain Nigeria 75/1. The stability of these recombinant viruses was assessed through consecutive passages in cell culture. Immunogenicity studies were carried out in both mice and sheep to assess the induction of cellular and humoral immune responses capable of providing protection against RVFV and PPRV. These studies included intracellular cytokine staining (ICS), IFN-γ ELISAs, standard ELISAs for antibody detection, and virus neutralization assays. Results: The recombinant RVFVs expressing PPRV H or F proteins demonstrated stability in cell culture, maintaining high viral titers and consistent transgene expression over four passages. Immunization of mice resulted in the production of serum antibodies capable of neutralizing both RVFV and PPRV in vitro as well as cell-mediated immune responses specific to PPRV and RVFV antigens. In mice vaccinated with a high dose (105 pfu), RVFV neutralizing titers reached ≥1:160 and PPRV neutralizing titers ranged from 1:40 to 1:80 by day 30 post-immunization. In sheep, neutralizing antibody titers against RVFV exceeded 1:160 as early as 2 days post-inoculation, while PPRV-specific neutralization titers reached up to 1:80 by day 21 in responsive individuals. In mice, administration of rZH548ΔNSs:FPPRV elicited a detectable CD8+ IFNγ+ T-cell response against PPRV, with levels ranging from 1.29% to 1.56% for the low and high doses, respectively. In sheep, rZH548ΔNSs:FPPRV also induced a robust IFNγ production against PPRV at 14 and 21 days post-infection (dpi). Conclusions: The successful generation and characterization of recombinant RVFVs expressing PPRV antigens demonstrate the potential of using rationally attenuated RVFV as a vector for multivalent vaccine development. Notably, the strategy proved more effective for the recombinant virus expressing the F protein, as it consistently induced more robust cellular and humoral immune responses. These results suggest that this approach could be a viable strategy for simultaneous immunization against Rift Valley fever and other prevalent ruminant diseases, such as peste des petits ruminants. Even though challenge studies were not performed in target species, the strong immune response observed supports including them in future studies. Full article
(This article belongs to the Special Issue Next-Generation Vaccines for Animal Infectious Diseases)
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23 pages, 489 KB  
Review
Japanese Encephalitis Vaccine in Low- and Middle-Income Countries (LMICs): A Narrative Review of Efficacy, Effectiveness, Safety, Cost, and Policy
by Eufrasia Ine Pilihanto, Btari Kalisha Nyratri, Muhammad Dafrizal Firdaus and Rano Kurnia Sinuraya
Vaccines 2025, 13(10), 1038; https://doi.org/10.3390/vaccines13101038 - 8 Oct 2025
Viewed by 595
Abstract
Japanese Encephalitis (JE) is a mosquito-borne viral infection that causes acute brain inflammation. First identified in Japan in 1871, the disease gained renewed global attention in 2025 after emerging in a non-endemic region, raising significant healthcare concerns. Vaccination remains the most effective strategy [...] Read more.
Japanese Encephalitis (JE) is a mosquito-borne viral infection that causes acute brain inflammation. First identified in Japan in 1871, the disease gained renewed global attention in 2025 after emerging in a non-endemic region, raising significant healthcare concerns. Vaccination remains the most effective strategy for preventing outbreaks. However, low- and middle-income countries (LMICs) face considerable challenges in implementing vaccination programs due to geographical, economic, and regulatory barriers. Most existing studies on JE vaccines (JEVs) have been conducted in higher-income countries, leaving critical gaps in data on efficacy and safety in LMIC settings. Furthermore, uncertainties surrounding cost-effectiveness make funding decisions more complex. This narrative review evaluates the current evidence on JE vaccination in LMICs, based on a literature search in PubMed and ScienceDirect covering 2005–2025. The review examines vaccine efficacy, safety, cost-effectiveness, and policy implementation. Findings show that JEVs demonstrate high efficacy and strong safety profiles, with mild adverse effects, most commonly fever. The live attenuated SA 14-14-2 vaccine (LAJEV) is particularly cost-effective, offering substantial economic benefits by reducing healthcare expenditures in endemic regions. To ensure sustainability, vaccination programs in LMICs require tailored policies and targeted financial support. Policy frameworks must be adapted to local contexts, enabling focused, effective, and equitable implementation. Full article
(This article belongs to the Section Vaccines and Public Health)
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10 pages, 739 KB  
Article
SARS-COV-2 Vaccination Response in Non-Domestic Species Housed at the Toronto Zoo
by Sara Pagliarani, Jaime Tuling, Phuc H. Pham, Alexander Leacy, Pauline Delnatte, Brandon N. Lillie, Nicholas Masters, Jamie Sookhoo, Shawn Babiuk, Sarah K. Wootton and Leonardo Susta
Vaccines 2025, 13(10), 1037; https://doi.org/10.3390/vaccines13101037 - 8 Oct 2025
Viewed by 332
Abstract
Background: Due to the wide host range of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), vaccination has been recommended for susceptible species in zoological collections, particularly to protect endangered species. The Zoetis® Experimental Mink Coronavirus Vaccine (Subunit) was temporarily authorized [...] Read more.
Background: Due to the wide host range of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), vaccination has been recommended for susceptible species in zoological collections, particularly to protect endangered species. The Zoetis® Experimental Mink Coronavirus Vaccine (Subunit) was temporarily authorized in 2021–2024 for emergency use in North America for this purpose. However, there are limited data regarding its safety or efficacy in non-domestic mammals. The present study was conducted to assess the ability of this vaccine to elicit serum neutralizing titers against SARS-CoV-2 in selected animals from the Toronto Zoo (TZ) vaccinated during 2022. Methods: Serum samples were collected from 24 individuals across four families (Cervidae, Felidae, Ursidae, and Hyaenidae) and tested using a surrogate virus neutralization test (sVNT) and a plaque-reduction neutralization test (PRNT). Results: The results showed that all species developed some neutralizing titers after at least one vaccine dose, except for polar bears, which showed no seroconversion. Felids and hyenas had the highest neutralizing titers, which peaked at 3 and declined between 4 and 6 months after boost. These differences may stem from species-specific immune responses or lack of vaccination protocols tailored to individual species. Conclusions: While natural infection with SARS-CoV-2 could not be ruled out in the cohort of this study, insights from our results have the potential to inform future vaccine recommendations for non-domestic species. Furthermore, our study highlighted the value of competitive assays in assessing serological responses across a broad range of exotic species, for which reagents, such as anti-isotype antibodies, are often unavailable. Full article
(This article belongs to the Collection COVID-19 Vaccine Development and Vaccination)
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