Vaccines

17 pages, 479 KB

Open AccessReview

Potency Evaluation and Predictive Quality Control System Construction Strategy for Respiratory Syncytial Virus mRNA Vaccines

by Su Zhang, Changgui Li and Yaru Quan

Vaccines 2026, 14(3), 199; https://doi.org/10.3390/vaccines14030199 - 24 Feb 2026

Abstract

The rapid advancement of respiratory syncytial virus (RSV) mRNA vaccines has created an urgent need for robust, standardized, and predictive potency evaluation systems. Currently, this field relies on diverse, non-standardized in vitro methods that lack quantitative correlations with in vivo immune protection. This [...] Read more.

The rapid advancement of respiratory syncytial virus (RSV) mRNA vaccines has created an urgent need for robust, standardized, and predictive potency evaluation systems. Currently, this field relies on diverse, non-standardized in vitro methods that lack quantitative correlations with in vivo immune protection. This poses significant challenges for vaccine process optimization, quality control, and regulatory review. This paper systematically analyzes the strengths and limitations of existing in vitro and in vivo assessment strategies, identifying a bottleneck in the current framework due to the absence of quantitative links between in vitro indicators and in vivo outcomes. It proposes that addressing these challenges hinges on establishing predictive in vitro–in vivo correlation (IVIVC). Furthermore, it outlines a feasible pathway for constructing such predictive models through the design of systematic experimental protocols and multivariate statistical analysis. Alignment with Quality by Design (QbD) principles, this strategy aims to transition potency evaluation from empirical exploration to a predictive, standardized framework, ultimately streamlining the lifecycle management of RSV mRNA vaccines. Full article

(This article belongs to the Section Nucleic Acid (DNA and mRNA) Vaccines)

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2 pages, 285 KB

Open AccessCorrection

Correction: Boikos et al. Co-Administration of BNT162b2 COVID-19 and Influenza Vaccines in Adults: A Global Systematic Review. Vaccines 2025, 13, 381

by Constantina Boikos, Kassandra Schaible, Solange Nunez-Gonzalez, Verna Welch, Tianyan Hu, Moe Hein Kyaw, Laura Elizabeth Choi, Joanna Kamar, Henry Goebe and John McLaughlin

Vaccines 2026, 14(3), 198; https://doi.org/10.3390/vaccines14030198 - 24 Feb 2026

Abstract

In the original publication [...] Full article

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20 pages, 3060 KB

Open AccessArticle

Innate Immunity Trained in the Protective Response of Vaccine Candidates Against Intracellular Pathogens

by Jefferson B. S. Oliveira, Laice A. Silva, Monique F. S. Sousa, Aldcejam M. F. Junior, Camila G. Almeida, Robson S. Barducci, Marcella P. Milazzotto, Humberto M. Brandão, Renato L. Santos and Tatiane A. Paixão

Vaccines 2026, 14(2), 197; https://doi.org/10.3390/vaccines14020197 - 23 Feb 2026

Abstract

Background/Objectives: Trained innate immunity refers to the enhanced responsiveness of innate immune cells, particularly macrophages, following exposure to stimuli such as β-glucan or zymosan, enabling improved defense against unrelated pathogens. This phenomenon has been widely investigated to better understand host–pathogen interactions and to [...] Read more.

Background/Objectives: Trained innate immunity refers to the enhanced responsiveness of innate immune cells, particularly macrophages, following exposure to stimuli such as β-glucan or zymosan, enabling improved defense against unrelated pathogens. This phenomenon has been widely investigated to better understand host–pathogen interactions and to support the development of improved infection control strategies. This study evaluated whether these training stimuli could enhance the protective efficacy of attenuated or inactivated vaccine models against Brucella ovis and Listeria monocytogenes infection. Methods: Trained innate immunity was induced in vivo using β-glucan or zymosan, and seven days later mice were vaccinated with attenuated or gamma-irradiated formulations and subsequently challenged with B. ovis or L. monocytogenes. Vaccine-induced protection and immune responses were assessed through multiple experimental approaches. Results: β-glucan significantly reduced bacterial infection in vitro in bone-marrow-derived macrophages and in vivo in target organs compared with zymosan. Although β-glucan did not enhance the efficacy of the attenuated B. ovis ΔabcBA vaccine, it markedly reduced bacterial colonization in mice vaccinated with gamma-irradiated B. ovis. β-glucan also did not improve the efficacy of the gamma-irradiated L. monocytogenes vaccine; however, 50% of the trained and vaccinated mice showed no detectable bacterial recovery. Increasing the number of β-glucan doses negatively affected infection control, suggesting that overstimulation may impair trained immunity. Conclusion: Trained innate immunity enhances the protective effect of inactivated experimental vaccines against B. ovis and L. monocytogenes, while exerting a detrimental influence on the efficacy of a live attenuated B. ovis vaccine model. Full article

(This article belongs to the Section Veterinary Vaccines)

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27 pages, 341 KB

Open AccessArticle

Knowledge, Attitudes, and Practices of Hungarian General Practitioners Regarding Human Papillomavirus (HPV) Infection and Vaccination: A Nationwide Cross-Sectional Study

by Richárd Tóth, Pál Sebok, Eszter Börzsönyi, Icó Tóth, Barbara Sebők, Balázs Vida, Ferenc Bánhidy, Márton Keszthelyi and Balázs Lintner

Vaccines 2026, 14(2), 196; https://doi.org/10.3390/vaccines14020196 - 22 Feb 2026

Abstract

Objective: To evaluate the level of knowledge, attitudes, and practices of Hungarian general practitioners (GPs) concerning human papillomavirus (HPV) infection, cervical cancer prevention, and HPV vaccination, and to identify physician-level factors associated with proactive recommendation practices. Methods: A cross-sectional nationwide survey [...] Read more.

Objective: To evaluate the level of knowledge, attitudes, and practices of Hungarian general practitioners (GPs) concerning human papillomavirus (HPV) infection, cervical cancer prevention, and HPV vaccination, and to identify physician-level factors associated with proactive recommendation practices. Methods: A cross-sectional nationwide survey was conducted between 30 April and 1 June 2024. The online questionnaire was distributed to practicing Hungarian GPs listed in the National Health Insurance Fund database. Anonymous responses were collected on demographic data, knowledge of HPV transmission and oncogenic potential, awareness of vaccination guidelines, and clinical counseling habits. Descriptive and inferential statistical analyses were performed. A total of 413 responses were received. Results: Most respondents were female (72.6%) with an average of 22.4 ± 9.6 years of professional experience. Although 89.8% correctly identified the causal link between HPV and cervical cancer, only 56.2% were aware of the complete vaccination schedule recommended for adolescents initiating after age 15. Knowledge scores were significantly higher among female physicians, urban practitioners, and those with postgraduate preventive medicine training. While the overall attitude toward HPV vaccination was positive (mean 4.6/5), 38.4% of respondents reported parental hesitancy as a common barrier, often citing misinformation regarding vaccine safety (64.9%) and lack of perceived need for boys (58.7%). Regression analysis revealed that familiarity with WHO and national vaccination guidelines independently predicted proactive vaccine recommendation (β = 0.43, p < 0.001). Conclusions: Hungarian general practitioners demonstrate good baseline awareness of HPV and its oncogenic role; however, knowledge gaps persist regarding vaccination schedules and counseling practices. Enhancing continuous medical education and communication training could strengthen GPs’ role as key advocates in HPV vaccine promotion. Full article

(This article belongs to the Special Issue Recent Research on Human Papillomavirus (HPV) Infection and Vaccination: 2nd Edition)

13 pages, 855 KB

Open AccessArticle

Evaluation of Antibodies Induced by Melanoma Helper Peptide Vaccine and Their Modulation by Vaccine Adjuvants

by Emily G. Ashkani, Anna M. Dickinson, Walter C. Olson, Justin J. Taylor and Craig L. Slingluff, Jr.

Vaccines 2026, 14(2), 195; https://doi.org/10.3390/vaccines14020195 - 21 Feb 2026

Abstract

Background/Objectives: Vaccines targeting melanoma antigens can elicit CD8⁺ T cell responses, but a growing body of work suggests CD4⁺ T cells also play a role in tumor control. Induction of CD4⁺ cells may also support B cells in producing tumor [...] Read more.

Background/Objectives: Vaccines targeting melanoma antigens can elicit CD8⁺ T cell responses, but a growing body of work suggests CD4⁺ T cells also play a role in tumor control. Induction of CD4⁺ cells may also support B cells in producing tumor antigen-specific antibodies (Abs). We investigated Abs induced by vaccination with a cocktail of six class II MHC-restricted melanoma peptides (6MHP) and the effect of adjuvant type on Ab isotypes. We hypothesized that the vaccines would induce Abs that respond to different epitopes on individual peptides and that IgG isotype distribution varies with different vaccine adjuvants. Methods: Sera from patients who received a 6MHP vaccine were evaluated with enzyme-linked immunosorbent assays to map epitopes for polyclonal Ab responses to synthetic melanoma peptides. IgG isotypes of Ab responses to 6MHP were assessed in patients who received one of four adjuvants (Incomplete Freund’s Adjuvant (IFA) alone, IFA + polyICLC, IFA + systemic metronomic cyclophosphamide (mCy), or IFA + polyICLC + systemic mCy) to characterize IgG isotype distribution. Results: Epitope mapping revealed that at least 50% of patients had responses to two or more epitopes on the same peptide, suggesting polyclonal Ab responses. Serum evaluation for IgG isotypes showed predominant induction of IgG1 and IgG3. Mean total IgG was highest when IFA and polyICLC were used in combination. Patients who received TLR3 agonist polyICLC had significantly higher concentrations of total IgG, IgG1, and IgG3 compared to patients who did not receive polyICLC. Conclusions: Vaccine-induced Abs may respond to multiple epitopes within the same peptide, warranting further studies into their ability to facilitate antigen uptake and presentation through the formation of large immune complexes. The findings also show that adding polyICLC to IFA can significantly enhance Ab responses. Collectively, this work underscores the immunologic potential of peptide-induced Abs and the importance of adjuvant selection in cancer vaccine design. Full article

(This article belongs to the Section Vaccination Against Cancer and Chronic Diseases)

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14 pages, 565 KB

Open AccessReview

Advances in HPV Vaccination in People Living with HIV: A Review

by Megan Mooberry, J. Brooks Jackson and Mary B. Rysavy

Vaccines 2026, 14(2), 194; https://doi.org/10.3390/vaccines14020194 - 21 Feb 2026

Abstract

Human papillomavirus (HPV) is the most common sexually transmitted infection worldwide and is a leading cause of cervical, anal, penile, and oropharyngeal cancers. This review summarizes the epidemiology of HPV and the immunogenicity, clinical efficacy, and current HPV vaccination recommendations among people living [...] Read more.

Human papillomavirus (HPV) is the most common sexually transmitted infection worldwide and is a leading cause of cervical, anal, penile, and oropharyngeal cancers. This review summarizes the epidemiology of HPV and the immunogenicity, clinical efficacy, and current HPV vaccination recommendations among people living with HIV (PLWH). PLWH experience a disproportionate burden of HPV-related infection and HPV-related malignancies. Although HPV vaccines have been shown to be highly effective, vaccination coverage among PLWH remains suboptimal, particularly in low- and middle-income countries. Barriers to vaccination include extended dosing schedules, limited awareness of the vaccine, and misinformation. Evidence indicates HPV vaccines are safe and induce a robust antibody response in PLWH, especially among individuals with higher CD4+ cell counts and viral suppression on antiretroviral therapy. However, evidence for reduction in clinical HPV-related disease in this population remains limited. Ongoing research is aimed at optimizing the HPV vaccination schedule for PLWH and expanding vaccination in older, high-risk subgroups. Integrating HPV vaccination into HIV care is essential to reduce HPV-related morbidity and mortality in PLWH. Full article

(This article belongs to the Special Issue Vaccines and Vaccination: HIV, Hepatitis Viruses, and HPV)

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22 pages, 1444 KB

Open AccessArticle

Oral Bait Immunization of Eurasian Wild Boar (Sus scrofa) Against African Swine Fever with “ASFV-G-ΔI177L”: Bait Performance, Immunogenicity, and Environmental Monitoring

by Jörg Beckmann, Sandra Blome, Nuria Bujan, Christian Gortázar, Theresa Holzum, Steffen Ortmann, David Relimpio, Alexander Schäfer, Elisenda Viaplana, Ad Vos and Virginia Friedrichs

Vaccines 2026, 14(2), 193; https://doi.org/10.3390/vaccines14020193 - 21 Feb 2026

Abstract

Background/Objectives: African swine fever is currently the most devastating viral disease affecting domestic and wild suids, causing major economic losses and severe impacts on natural populations. Oral immunization could become an important tool to control the panzootic and support wild pig conservation. [...] Read more.

Background/Objectives: African swine fever is currently the most devastating viral disease affecting domestic and wild suids, causing major economic losses and severe impacts on natural populations. Oral immunization could become an important tool to control the panzootic and support wild pig conservation. However, this requires safe and effective vaccines, baits accepted by target species, and vaccine reservoirs that reliably release the vaccine during bait intake while maintaining vaccine integrity. Methods: We evaluated different bait types and vaccine containers in four wild Suiformes species, including Eurasian wild boar. In the same wild boar, we assessed oral vaccination with the live attenuated vaccine candidate “ASFV-G-ΔI177L”. Environmental monitoring approaches were applied to detect potential virus shedding, and vaccine immunogenicity and dissemination were evaluated. Vaccine stability was tested in vitro in two container types under different temperature conditions. Results: Bait uptake and container performance varied between manufacturers and among species. Environmental samples were largely negative for vaccine virus genome under controlled laboratory conditions, with only a few positive cotton ropes (0.43% of all samples). After oral bait vaccination, 45% (9/20) of wild boar seroconverted, with a higher proportion in animals receiving the vaccine in the slightly less attractive bait (gelatine-based). Vaccine virus dissemination was limited to a small number of organs, including gastrohepatic and mandibular lymph nodes. Conclusions: Our findings demonstrate that wild pigs can be vaccinated orally with “ASFV-G-ΔI177L” while virus shedding appears minimal. Although the tested baits show potential for multiple target species, baits and containers require optimization. Environmental monitoring methods also need refinement for field application. Full article

(This article belongs to the Special Issue Control Strategies and Vaccines for African Swine Fever—What Is to Come)

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16 pages, 2005 KB

Open AccessArticle

Carrier-Protein-Free Pneumococcal Glycoconjugate Vaccines Enabled by SPAAC: Serotype 15C CPS–PADRE Conjugates and the Impact of an RR Cleavage Motif

by Huimin Yang, Zeyu Liao, Yingjie Zhong, Qi Gao, Hangqi Zhang and Chengli Zong

Vaccines 2026, 14(2), 192; https://doi.org/10.3390/vaccines14020192 - 19 Feb 2026

Abstract

Background/Objectives: Polysaccharide-protein conjugate vaccines have proven highly effective, yet they remain limited by manufacturing complexity, cost, and variable performance across serotypes, while carrier proteins can add unwanted immunological and production burdens. To address these constraints, we explored a carrier-protein-free conjugate vaccine concept in [...] Read more.

Background/Objectives: Polysaccharide-protein conjugate vaccines have proven highly effective, yet they remain limited by manufacturing complexity, cost, and variable performance across serotypes, while carrier proteins can add unwanted immunological and production burdens. To address these constraints, we explored a carrier-protein-free conjugate vaccine concept in which a broadly MHC class II-binding helper epitope (PADRE) replaces the conventional protein carrier to provide T-cell help for a pneumococcal capsular polysaccharide antigen. Methods: Using serotype 15C CPS as a model, we generated CPS–PADRE conjugates and compared designs with or without a putative cleavable motif (RR) at the junction, alongside a conventional protein conjugate as a benchmark. Results: In mice, the CPS–protein conjugate induced the strongest CPS-specific IgG response, whereas CPS–PADRE conjugates elicited clear but overall lower antibody levels. Notably, incorporation of the cleavable motif did not improve immunogenicity and instead reduced humoral responses relative to the non-cleavable design. Conclusion: These findings support the feasibility of carrier-protein-free polysaccharide-peptide conjugate vaccines, while highlighting that cleavable junctions are not universally advantageous and must be empirically optimized for polysaccharide-helper epitope architectures. Full article

(This article belongs to the Special Issue Protective Immunity and Adjuvant Vaccines)

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18 pages, 499 KB

Open AccessArticle

Community Perceptions and Attitudes Toward Vaccination in Madagascar

by Maharisoa Ralambosoa, Amandine Oleffe, Vatsiharizandry Mandrosovololona, Zo Patricia Rasolomanana, Lethicia Lydia Yasmine, Paubert Tsivahiny, Mamy Andrianirina Rakotondratsara and Laurent Musango

Vaccines 2026, 14(2), 191; https://doi.org/10.3390/vaccines14020191 - 19 Feb 2026

Abstract

Background/Objectives: Low vaccination coverage and the persistence of zero-dose children remain the principal challenges for immunization efforts in Madagascar. To address these barriers, a socio-anthropological study was conducted to identify the determinants of both vaccination and non-vaccination in eight districts of the [...] Read more.

Background/Objectives: Low vaccination coverage and the persistence of zero-dose children remain the principal challenges for immunization efforts in Madagascar. To address these barriers, a socio-anthropological study was conducted to identify the determinants of both vaccination and non-vaccination in eight districts of the country. Methods: District selection was based primarily on immunization performance—specifically the proportion of zero-dose children—along with criteria of geographic and cultural diversity. A qualitative approach was employed, comprising 162 semi-structured individual interviews and 41 focus group discussions with key informants, including political–administrative, religious, and traditional authorities, healthcare workers, community health workers, and parents. Results: Overall, the benefits of vaccination were widely acknowledged by the population. Anti-vaccine rumors were found to be sporadic and, due to their provisional nature, potentially reversible even among those who relay them. Beyond conventional barriers such as scheduling constraints and limited accessibility, fluctuating motivation among community health workers and structural challenges affecting their work emerged as notable findings. Conversely, factors promoting vaccine acceptance were associated with trust in the vaccinators themselves and with a good understanding of vaccination-related issues, fostered through increased and context-specific sensitization efforts. Conclusions: In conclusion, no evidence was found to associate contexts such as rural settings or low-performing vaccination areas with lower vaccine acceptance. Similarly, anti-vaccine rumors were not confined to any particular category or group. Ultimately, the main obstacles are the prioritization of economic risk and concerns about potential side effects. The primary recommendation concerns strengthening awareness-raising efforts, while strengthening trust and improving the working conditions of community health workers. Full article

(This article belongs to the Section Vaccines and Public Health)

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19 pages, 2231 KB

Open AccessArticle

Vaccination with Carbapenemase KPC-2 and Virulence Factor Pal Provided Robust Protection Against Klebsiella pneumoniae Lung Infection

by Shichun Jiang, Yue Yuan, Yuanda Tang, Jingwen Liao, Zhifu Chen, Xiaoqian Yu, Jing Zhu, Qiang Gou, Haiming Jing, Xiaoyu Li, Zhuo Zhao, Yongxue Xu, Quanming Zou and Jinyong Zhang

Vaccines 2026, 14(2), 190; https://doi.org/10.3390/vaccines14020190 - 19 Feb 2026

Abstract

Objectives: Carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) merges multidrug resistance with hypervirulence, posing unprecedented therapeutic challenges. This study aimed to evaluate the efficacy of a recombinant fusion protein vaccine, KPC-Pal, designed to target both the carbapenemase KPC-2 and the virulence-associated peptidoglycan-associated lipoprotein Pal. [...] Read more.

Objectives: Carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) merges multidrug resistance with hypervirulence, posing unprecedented therapeutic challenges. This study aimed to evaluate the efficacy of a recombinant fusion protein vaccine, KPC-Pal, designed to target both the carbapenemase KPC-2 and the virulence-associated peptidoglycan-associated lipoprotein Pal. Methods: The KPC-Pal fusion protein was constructed, expressed, and purified. Its protective efficacy was systematically assessed in a murine pneumonia model by measuring antigen-specific antibodies, cytokine profiles, and memory cell populations. The synergistic effect with the antibiotic meropenem was evaluated both in vitro and in vivo. Furthermore, the interaction with innate immune signaling via TLR2 was investigated. Results: Immunization with KPC-Pal conferred superior protection, resulting in significantly higher survival rates and reduced bacterial burdens in the lungs compared to immunization with either KPC-2 or Pal alone. It induced a robust Th2-biased humoral response and a mixed Th1/Th2/Th17 cellular immune profile, along with enhanced formation of tissue-resident memory T cells. Antibodies generated against KPC-Pal enhanced the efficacy of meropenem in vitro and in animal models, demonstrating a synergistic effect. While Pal alone strongly activated TLR2-driven inflammatory pathways, the KPC-Pal fusion selectively modulated MAPK signaling, mitigating excessive cytokine production. Additionally, KPC-Pal vaccination elicited cross-reactive antibodies against KPC-3 and KPC-33 variants. Conclusions: KPC-Pal functions as both an antigen and a self-adjuvant, offering a promising dual-target strategy for combating K. pneumoniae infections. Full article

(This article belongs to the Section Vaccine Design, Development, and Delivery)

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36 pages, 1671 KB

Open AccessReview

Therapeutic Strategies for Hepatocellular Carcinoma: Current Advances and Future Perspectives

by Palaniyandi Muthukutty, Jeong Heo and So Young Yoo

Vaccines 2026, 14(2), 189; https://doi.org/10.3390/vaccines14020189 - 18 Feb 2026

Abstract

Hepatocellular carcinoma (HCC) accounts for approximately 90% of primary liver cancers and remains a leading cause of cancer-related mortality worldwide. The management of HCC poses a major therapeutic challenge due to its pronounced molecular heterogeneity, frequent late-stage diagnosis, and intrinsic resistance to both [...] Read more.

Hepatocellular carcinoma (HCC) accounts for approximately 90% of primary liver cancers and remains a leading cause of cancer-related mortality worldwide. The management of HCC poses a major therapeutic challenge due to its pronounced molecular heterogeneity, frequent late-stage diagnosis, and intrinsic resistance to both conventional and modern therapeutic modalities. Furthermore, the relatively low tumor mutational burden and the presence of a profoundly immunosuppressive tumor microenvironment (TME) substantially limit the efficacy of immune-based interventions, particularly in advanced disease stages. In recent years, novel immunotherapeutic approaches—including immune checkpoint blockade (ICB), oncolytic virus therapy, and genetically engineered immune cell-based therapies—have garnered significant attention. Nevertheless, durable clinical responses and meaningful improvements in overall survival remain limited, underscoring the complexity of achieving effective immune control in HCC. Emerging evidence suggests that rational combination immunotherapy strategies may offer new therapeutic opportunities by overcoming immune resistance mechanisms. In this review, we provide a comprehensive overview of current therapeutic strategies for HCC, with particular emphasis on immunotherapeutic approaches. We discuss common clinical challenges spanning diagnosis to treatment resistance, critically evaluate key clinical trial outcomes, and highlight future directions aimed at improving therapeutic efficacy and long-term disease control. Full article

(This article belongs to the Section Vaccination Against Cancer and Chronic Diseases)

20 pages, 760 KB

Open AccessArticle

A Multi-Country Comparison of Number Needed to Vaccinate for PCV20 and PCV15 in Infants

by Euan Dawson, Maria J. Tort, An Ta and Mark H. Rozenbaum

Vaccines 2026, 14(2), 188; https://doi.org/10.3390/vaccines14020188 - 18 Feb 2026

Abstract

Background/Objectives: Infant pneumococcal conjugate vaccines (PCV) have significantly reduced pneumococcal morbidity and mortality. Newer vaccines, 15-valent (PCV15) and 20-valent (PCV20), offer broader serotype coverage, potentially preventing more disease. This study estimated the number needed to vaccinate (NNV) to prevent one disease outcome for [...] Read more.

Background/Objectives: Infant pneumococcal conjugate vaccines (PCV) have significantly reduced pneumococcal morbidity and mortality. Newer vaccines, 15-valent (PCV15) and 20-valent (PCV20), offer broader serotype coverage, potentially preventing more disease. This study estimated the number needed to vaccinate (NNV) to prevent one disease outcome for infant PCV20 and PCV15 programs versus 13-valent PCV (PCV13). Countries from Europe, the Asia-Pacific, and the Americas were included. Methods: A multi-cohort, population-based model estimated the cumulative NNVs for infant programs with PCV20 and PCV15 relative to PCV13 in 21 countries. Outcomes included overall pneumococcal case, hospitalization, and death. The ratio of PCV15 NNVs to PCV20 NNVs was calculated. Probabilistic sensitivity analysis (PSA) and scenario assessments tested results’ robustness. Results: Across 21 countries, the median of country-specific NNV estimates to prevent one pneumococcal case was 13 with PCV20 and 80 with PCV15. Median NNVs to prevent a hospitalization or death were 44 and 568 with PCV20 and 203 and 2203 with PCV15, respectively. PCV20 demonstrated lower NNVs than PCV15 across all countries and outcomes. Median NNV ratios for PCV15 versus PCV20 were 5.1 (case), 4.5 (hospitalization), and 4.2 (death). No clear geographic differences were observed. PSA and scenario analyses indicated stable results with minimal deviations. Conclusions: Infant immunization with PCV20 is associated with lower NNVs than PCV15. To achieve the same disease reduction as PCV20, over five times as many children would need to be vaccinated with PCV15. These findings suggest PCV20 may offer greater public health impact compared with PCV15 in infant immunization programs. Full article

(This article belongs to the Special Issue Streptococcal Vaccines: Current Status and Future Directions)

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20 pages, 2634 KB

Open AccessArticle

Vaccination with an African Swine Fever Virus Multiepitope Protein Chitosan Nanoparticle-Based Subunit Vaccine Elicits Robust Immune Responses In Vivo

by Carolyn M. Lee, Raksha Suresh, Patricia A. Boley, Olaitan Comfort Shekoni, Jennifer Schrock, Sara Dolatyabi, Mithilesh Singh, Saroj Khatiwada, Kush Kumar Yadav, Dina Bugybayeva, Juliette Hanson, Renukaradhya J. Gourapura and Scott P. Kenney

Vaccines 2026, 14(2), 187; https://doi.org/10.3390/vaccines14020187 - 17 Feb 2026

Abstract

Background/Objectives: African swine fever virus (ASFV), the causative agent of African swine fever (ASF), is a highly contagious virus affecting both domestic and feral pig populations with mortality rates approaching 100% within one week of infection. Currently, there are limited treatments or vaccines [...] Read more.

Background/Objectives: African swine fever virus (ASFV), the causative agent of African swine fever (ASF), is a highly contagious virus affecting both domestic and feral pig populations with mortality rates approaching 100% within one week of infection. Currently, there are limited treatments or vaccines available to control the disease. Although ASF is endemic in sub-Saharan Africa, the virus has also spread widely, reaching regions of the European Union, Russia, China, Southeast Asia, and, more recently, to the Dominican Republic and Haiti, bringing the threat closer to the United States (U.S.). ASF introduction to the U.S. would have severe consequences for swine producers and the national pork industry. Consequently, there is an urgent need to develop effective vaccine strategies to manage ongoing outbreaks abroad and mitigate the risk of future ASF incursions. Recent efforts have identified several ASFV epitopes and evaluated them in experimental vaccine trials. However, these vaccine candidates have elicited limited protective immune responses and have not demonstrated full protective efficacy. Methods: In this study, we employed in silico modeling and epitope prediction tools to design a synthetic multiepitope ASF protein incorporating key immunogenic regions of ASFV. The goal was to generate a single-antigen construct capable of inducing broad and robust immune responses when formulated with an established nanoparticle-based vaccine platform. The multiepitope ASF protein was subsequently expressed and entrapped into mannose-conjugated chitosan (M-CS) nanoparticles for vaccine formulation. The candidate vaccine, formulated with M-CS nanoparticle-entrapped adjuvant (ADU S100), was administered intramuscularly to pigs, and both T- and B-cell responses were assessed following the primary (DPV 22) and booster (DPV 42) doses. Results: Our M-CS ASF protein vaccine elicited antigen-specific T- and B-cell responses, both of which are recognized as central correlates of protection against ASFV. Conclusions: These promising preliminary immunological findings suggest that this nanoparticle vaccine has the potential to confer protection against ASFV challenge, a hypothesis that will be examined in future studies. Full article

(This article belongs to the Special Issue African Swine Fever Virus Immunotherapies and Vaccine Development)

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16 pages, 2162 KB

Open AccessArticle

Comparative Evaluation of Mucosal Adjuvants for Intranasal Immunization with a Recombinant RSV Prefusion F Protein

by Hongqiao Hu, Lei Cao, Jie Jiang, Yuqing Shi, Liang Du, Mengxuan Chu, Hai Li and Yan Zhang

Vaccines 2026, 14(2), 186; https://doi.org/10.3390/vaccines14020186 - 16 Feb 2026

Abstract

Background: Respiratory syncytial virus (RSV) remains a major etiologic agent of acute lower respiratory tract infection (ALRTI). Currently licensed RSV vaccines are administered by intramuscular injection and induce limited immunity at the respiratory mucosal interface, underscoring the need for effective mucosal vaccination strategies. [...] Read more.

Background: Respiratory syncytial virus (RSV) remains a major etiologic agent of acute lower respiratory tract infection (ALRTI). Currently licensed RSV vaccines are administered by intramuscular injection and induce limited immunity at the respiratory mucosal interface, underscoring the need for effective mucosal vaccination strategies. Methods: To enhance mucosal immune responses, we used prefusion F protein (Pre-F) as the antigen and performed intranasal immunization in BALB/c mice. Four mucosal adjuvants (CpG-ODN, CTA1-DD, IFN-α, and PEI) were systematically compared across different dose levels to evaluate their immunological and protective efficacy. Results: Both adjuvant type and dose helped shape the magnitude and quality of the immune response and the level of protection. CpG-ODN showed a dose-restricted immunopotentiating effect: an intermediate dose (10 µg) significantly increased neutralizing antibody titers and nasal mucosal IgA responses, improved post-challenge body weight recovery, and reduced lung viral load, whereas higher doses provided no additional benefit and were associated with aggravated lung pathology. PEI and IFN-α exhibited dose-dependency within a certain range, but increasing doses did not result in further improvements in immune responses or protection; an intermediate dose (10 µg) was sufficient to elicit robust systemic and mucosal immunity. CTA1-DD improved selected immune parameters at appropriate doses, yet its overall immunopotentiating effects remained modest. Direct comparative analysis using the representative doses selected from the three dose levels for each adjuvant indicated that 10 µg CpG-ODN or PEI provided superior immunogenicity and protection, whereas PEI induced a Th2-biased immune profile at both humoral and cellular levels. Conclusions: These findings highlight that favorable immunogenicity and protection are achieved within defined dose windows rather than at maximal doses. Among the adjuvants studied, low-to-intermediate doses of CpG-ODN, particularly 10 µg, show strong potential for intranasal mucosal immunization with recombinant RSV Pre-F protein. By systematically comparing dose–effect profiles across multiple mucosal adjuvants, this study offers comparative insights into adjuvant selection and dose selection for intranasal RSV vaccine development. Full article

(This article belongs to the Section Vaccines, Clinical Advancement, and Associated Immunology)

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15 pages, 3840 KB

Open AccessArticle

Comparison of Immune Cell Transfection by Different Vaccine Vectors After Intradermal Injection

by Jiani Liu, Destin T. Hinson, Michael J. Hansen, Virginia P. Van Keulen, Brian J. Parrett, Larry R. Pease and Michael A. Barry

Vaccines 2026, 14(2), 185; https://doi.org/10.3390/vaccines14020185 - 16 Feb 2026

Abstract

Background/Objectives: Antigen presenting cells (APCs) and immune cells have unique properties to drive or suppress immune responses. They are therefore key targets for the expression of vaccine antigens or transgene proteins. To better determine the utility of different molecular therapies to modify [...] Read more.

Background/Objectives: Antigen presenting cells (APCs) and immune cells have unique properties to drive or suppress immune responses. They are therefore key targets for the expression of vaccine antigens or transgene proteins. To better determine the utility of different molecular therapies to modify these cells, mRNA and DNA-based molecular therapy vectors were compared for their ability to genetically modify immune cells after intradermal injections in mice. DNA-based vectors included naked plasmid DNA, plasmid packaged in lipid nanoparticles (LNPs), and replication-defective adenovirus (Ad) vectors. mRNA delivery was mediated by packaging into LNPs like those used in COVID-19 vaccines. Methods: Each vector was used to deliver Cre recombinase into Cre reporter mice whose cells were activated to express green fluorescent protein (GFP) and firefly luciferase after Cre recombination. The mice were injected intradermally (ID) near the base of their tail at a site that drains into the inguinal lymph node. Luciferase activity was imaged in the living mice 1 or 4 days after vector injection. The animals were then euthanized, and luciferase activity was imaged in the draining inguinal lymph node. Cells were prepared from the intradermal injection site and from the draining lymph node to determine which immune cells were genetically modified by phenotyping CD45, CD3, and CD11b GFP-positive cells by flow cytometry. Given that the skin uniquely contains Langerhans dendritic cells, these CD207⁺ cells were also phenotyped in skin samples and in the draining lymph node. Results: In both the skin and in the draining lymph node, the rank order of luciferase and GFP activation by the vectors were: (1) Ad; (2) mRNA-LNP; (3) DNA-LNP; and (4) naked DNA. Only mRNA-LNP and Ad vectors mediated obvious luciferase activity in the living animals and in the draining lymph nodes by imaging. Notably, both vectors appeared to leak from the ID injection site and not only modify the draining lymph node but also strongly modify the livers of the mice. Naked DNA and DNA-LNP mediated detectable GFP activation in the skin and draining lymph node in some mice, but this activity was low and did not reach statistical significance when compared to PBS-treated animals. mRNA-LNPs and Ad both mediated significant Cre delivery in CD45⁺, CD3⁺, CD11b⁺, and CD207⁺ immune cells in the skin and in the lymph node, with adenovirus mediating consistently higher levels of expression in all of the tested cells. Conclusions: These data indicate that mRNA-LNP and Ad vectors mediate stronger modification of skin and lymph node immune cells after intradermal injections. Naked DNA and DNA-LNPs were markedly less potent at this activity than the other vectors. These data are consistent with the higher vaccine potency of mRNA-LNP and Ad vectors and suggest that approaches that increase targeting of immune cell subsets may have utility to increase efficacy while also reducing off-target modification of tissues like the liver. Full article

(This article belongs to the Section Vaccine Design, Development, and Delivery)

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15 pages, 3164 KB

Open AccessArticle

Immunization Against a Conserved Short 13-Amino Acid Receptor-Binding Epitope of FSHβ Reduces Spermatogenesis and Sperm Motility in Male Mice

by Xuanti Liu, Like Ran, Jingyi He, Shuhan Lei, Jiayi Zhang, Zongrui Yang and Xingfa Han

Vaccines 2026, 14(2), 184; https://doi.org/10.3390/vaccines14020184 - 15 Feb 2026

Abstract

Background: Follicle-stimulating hormone (FSH)-based vaccines show the potential to disrupt spermatogenesis without disturbing sexual function and libido in males. Herein, we developed a novel FSH vaccine based on the tandem of a conserved 13-amino acid receptor-binding epitope of FSHβ (FSHβ13AA-T) and tested its [...] Read more.

Background: Follicle-stimulating hormone (FSH)-based vaccines show the potential to disrupt spermatogenesis without disturbing sexual function and libido in males. Herein, we developed a novel FSH vaccine based on the tandem of a conserved 13-amino acid receptor-binding epitope of FSHβ (FSHβ13AA-T) and tested its effect on reproductive physiology and function using the male mouse as a model. Methods: Serum reproductive hormone levels, testicular histology, daily sperm production, sperm motility, libido and fertility of male mice following FSH vaccination were determined. Results: Compared to placebo-immunized controls, FSH vaccination triggered (p < 0.05) marked antibody generation, inhibited spermatogenesis and reduced sperm motility (p < 0.05), without adverse effects on serum LH and testosterone levels as well as the libido of male mice. Mechanistically, FSH vaccination suppressed (p < 0.05) testicular local estrogen production by downregulated aromatase encoding gene Cyp19a1 expression and also downregulated (p < 0.05) expression of key spermatogenic genes in testes, including Creb, INHα, Wnt2, Aqp8, Cmtm2a and Spata19, thus disrupting and impairing spermatogenesis and sperm motility. Conclusions: These results demonstrate that immunization of male mice against FSHβ13AA could substantially inhibit spermatogenesis and reduce sperm motility. Thus, FSHβ13AA-based vaccines hold potential for development as male contraceptives that do not compromise libido in species including men in which FSH is essential for spermatogenesis. Full article

(This article belongs to the Special Issue Innovations in Vaccine Technology)

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20 pages, 1430 KB

Open AccessReview

Impact of Vaccines Across the Lifespan: A New Perspective in Public Health—Conclusions of an Expert Panel—Part 1

by Roberto Debbag, María L. Ávila-Agüero, José Brea, Carlos Espinal, Rodrigo Romero-Feregrino, Jaime R. Torres, Hebe Vázquez, Robinson Cuadros, Gustavo Lazo-Páez, Andrea Schilling, Pablo Bonvehí, Maisa Kairalla and Alfonso J. Rodríguez-Morales

Vaccines 2026, 14(2), 183; https://doi.org/10.3390/vaccines14020183 - 15 Feb 2026

Abstract

Population aging is the most significant demographic transformation of the 21st century, reshaping health systems, economies, and societies. The biological processes of immunosenescence and inflammaging weaken host defenses, reduce vaccine effectiveness, and increase vulnerability to infectious and chronic diseases. These changes underscore the [...] Read more.

Population aging is the most significant demographic transformation of the 21st century, reshaping health systems, economies, and societies. The biological processes of immunosenescence and inflammaging weaken host defenses, reduce vaccine effectiveness, and increase vulnerability to infectious and chronic diseases. These changes underscore the urgent need for preventive strategies that extend beyond childhood immunization. Vaccination is a cornerstone of healthy aging, capable of preventing infections and has been associated with reductions in systemic inflammation, frailty, and loss of functional independence in later life. Furthermore, new insights into vaccine-mediated immunomodulation, including trained immunity, adjuvanted formulations, and epigenetic reprogramming, highlight the evolving role of vaccines as modulators of immune fitness across the lifespan. This first part of our review examines the intersection of aging and immunity, as well as the potential of vaccines to address these challenges. Part 2 will expand on specific vaccines, proposed vaccination schedules, and global perspectives for lifelong immunization. Full article

(This article belongs to the Special Issue Vaccine Development and Global Health)

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14 pages, 480 KB

Open AccessArticle

Impact of Seasonal Nirsevimab Administration in Infants Born During the RSV Circulation Period on RSV-Related Hospitalizations: A Population-Based Study from Emilia-Romagna, Northern Italy

by Susanna Esposito, Matteo Puntoni, Giuseppe Maglietta, Alessandro De Fanti, Chiara Ghizzi, Giacomo Biasucci, Federico Marchetti, Melodie Olivia Aricò, Gianluca Vergine, Marcello Stella, Battista Guidi, Agnese Suppiej, Francesca Alberghi, Emanuele Filice, Maria Elena Capra, Enrico Valletta, Andrea Miceli, Cristina Malaventura, Beatrice Rita Campana, Valentina Fainardi, Caterina Caminiti and Emilia-Romagna Paediatric COVID-19 Network Show full author list Hide full author list

Vaccines 2026, 14(2), 182; https://doi.org/10.3390/vaccines14020182 - 14 Feb 2026

Abstract

Background: Respiratory syncytial virus (RSV) is a leading cause of hospitalization in early infancy, with the greatest burden occurring in the first months of life. Following the COVID-19 pandemic, many countries experienced intensified RSV circulation. Nirsevimab, a long-acting monoclonal antibody providing season-long protection [...] Read more.

Background: Respiratory syncytial virus (RSV) is a leading cause of hospitalization in early infancy, with the greatest burden occurring in the first months of life. Following the COVID-19 pandemic, many countries experienced intensified RSV circulation. Nirsevimab, a long-acting monoclonal antibody providing season-long protection after a single dose, was introduced in Italy for the 2024–2025 RSV season and recommended for infants born during the period of RSV circulation. We evaluated the population-level impact of this seasonal nirsevimab strategy on RSV-related hospitalizations among young infants. Methods: We conducted a population-based observational study using regional hospital discharge records from Emilia-Romagna, Northern Italy, spanning January 2017 to April 2025. Analyses were restricted to RSV seasons (October–March) and infants aged ≤180 days. RSV-related hospitalizations were identified using ICD-9-CM codes. Hospitalization rates were calculated per 100,000 person-days. Incidence rate ratios (IRRs) were estimated using negative binomial regression models adjusted for season, age group, and sex, with clustering at the hospital level. The post-nirsevimab season (2024–2025) was compared with the immediate pre-nirsevimab season (2023–2024) and a pre-COVID reference season (2018–2019). Results: A total of 551 RSV hospitalizations occurred in the pre-COVID season, 753 in the pre-nirsevimab season, and 252 in the post-nirsevimab season. The post-nirsevimab season was associated with a substantial reduction in RSV-related hospitalization rates compared with both the pre-COVID season (IRR 0.52; 95% CI 0.41–0.66) and the pre-nirsevimab season (IRR 0.36; 95% CI 0.29–0.44). Reductions were observed consistently across epidemic months and were most pronounced during the first three to four months of life. Conclusions: Seasonal administration of nirsevimab to infants born during the RSV circulation period was associated with a marked and sustained reduction in RSV-related hospitalizations in early infancy. These findings support the effectiveness of targeted, seasonally timed infant immunoprophylaxis as a population-level RSV prevention strategy. Full article

(This article belongs to the Section Epidemiology and Vaccination)

25 pages, 537 KB

Open AccessArticle

Immunogenic Properties and Safety of a Quadrivalent Inactivated Subunit Adjuvanted Influenza Vaccine in Adults Aged 18 to 85 Years at the End of the COVID-19 Pandemic in the 2022–2023 Season

by Mikhail P. Kostinov, Aristitsa M. Kostinova, Sofia Iushkova, Lilia Gladkova, Anna Vlasenko, Yulia Dagil, Maria Kvasova, Anastasia Kameleva, Anastasia Kachnova, Irina Solovеva, Anna Khamidulina, Ekaterina Prutskova, Irina Mekhantseva, Natalia Andreeva, Valentina B. Polishchuk, Yvette Albahansa Mana and Anton M. Kostinov

Vaccines 2026, 14(2), 181; https://doi.org/10.3390/vaccines14020181 - 14 Feb 2026

Abstract

Background: SARS-CoV-2 infection has raised concerns about altered immune responses, creating a need to evaluate influenza vaccine performance in the post-COVID period. This study aimed to compare the immunogenicity and safety of a quadrivalent inactivated subunit adjuvanted influenza vaccine in adults aged [...] Read more.

Background: SARS-CoV-2 infection has raised concerns about altered immune responses, creating a need to evaluate influenza vaccine performance in the post-COVID period. This study aimed to compare the immunogenicity and safety of a quadrivalent inactivated subunit adjuvanted influenza vaccine in adults aged 18–85 years during the 2022–2023 season. Methods: A total of 144 adults were enrolled: group 1, aged 18–59 years (n = 124), and group 2, aged 60–85 years (n = 20). All received a quadrivalent inactivated subunit adjuvanted vaccine containing 5 μg of each influenza antigen and 500 μg of Azoximer bromide. IgG antibodies to vaccine strains were measured at baseline and days 30–32 using the hemagglutination inhibition assay. Participants were actively monitored for adverse events by telephone. Results: The Geometric Mean Fold Increase (GMFI) met the efficacy criteria in both age groups (≥2.5 for 18–59 years and ≥2.0 for 60–85 years), with no significant differences. The seroprotection rate reached accepted thresholds for most strains but was below criteria for B/Victoria in the 18–59 group (48%) and for B/Phuket in the 60–85 group (35%). Significant between-group differences were observed for B/Victoria (p = 0.01) and B/Phuket (p = 0.007). Seroconversion met criteria for all strains in younger adults, but for older adults, it was insufficient for B/Phuket (20%, below the ≥30% threshold; p = 0.05 vs. 18–59 years). Local reactions occurred in 24.2% and systemic in 11.3% of younger adults; in older adults, in 20% and 15%, respectively. All resolved spontaneously within 1–3 days. Conclusions: The quadrivalent adjuvanted influenza vaccine demonstrated acceptable immunogenicity and safety in adults aged 18–85 years despite potential post-COVID immune alterations. Full article

(This article belongs to the Section Vaccine Advancement, Efficacy and Safety)

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