Vaccines

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

Viewed by 680

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

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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

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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

Cited by 1 | Viewed by 966

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

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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

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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

Viewed by 590

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

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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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35 pages, 1659 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

Viewed by 1042

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)

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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

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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

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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

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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

Viewed by 827

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

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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

Cited by 1 | Viewed by 1767

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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13 pages, 647 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 and Caterina Caminiti Show full author list Hide full author list

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

Viewed by 801

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)

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24 pages, 1580 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

Viewed by 702

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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27 pages, 498 KB

Open AccessReview

Human Papillomavirus in Reproductive Health and Pregnancy: Clinical Implications, Outcomes, and a Comprehensive Review of Vaccination

by Hasan Volkan Ege, Charlotte Goutallier, Laura Burney Ellis, Houssein El Hajj, Joanna Kacperczyk-Bartnik, Bilal Esat Temiz, Nadja Taumberger, Reda Hemida, Gökçen Ege, Utku Akgör, Zvi Vaknin, Maria Kyrgiou and Murat Gultekin

Vaccines 2026, 14(2), 180; https://doi.org/10.3390/vaccines14020180 - 14 Feb 2026

Viewed by 1504

Abstract

Background/Objectives: Human papillomavirus (HPV) is the most common sexually transmitted virus worldwide and is frequently detected in women of reproductive age. In this population, HPV-related diseases and their management may affect reproductive health and pregnancy outcomes. This narrative review summarizes the current evidence [...] Read more.

Background/Objectives: Human papillomavirus (HPV) is the most common sexually transmitted virus worldwide and is frequently detected in women of reproductive age. In this population, HPV-related diseases and their management may affect reproductive health and pregnancy outcomes. This narrative review summarizes the current evidence on HPV infection and HPV-related diseases in relation to fertility, pregnancy, and neonatal outcomes, and discusses preventive strategies, with a particular focus on HPV vaccination. Methods: An international, multidisciplinary team of clinicians from the European Society of Gynaecological Oncology (ESGO) Prevention Committee reviewed the literature on HPV, HPV-related diseases, HPV vaccination, and reproductive outcomes, without time restrictions, prioritizing studies judged to meaningfully reflect the available evidence. Results: The most consistent evidence linking HPV-related conditions to adverse pregnancy outcomes relates to the treatment of cervical precancer, particularly excisional procedures, which are associated with an increased risk of preterm birth and mid-trimester pregnancy loss. In contrast, evidence that maternal HPV detection alone causes adverse pregnancy or neonatal outcomes remains limited and inconsistent. Data on HPV infection and subfertility are scarce and heterogeneous. Management of HPV-related lesions during pregnancy remains challenging and requires careful balancing of maternal safety with avoidance of unnecessary interventions. HPV DNA has been detected in neonatal samples, but convincing evidence for clinically relevant vertical transmission is lacking. Available data indicate that inadvertent HPV vaccination shortly before or during pregnancy is not associated with adverse pregnancy outcomes. Conclusions: Current evidence suggests that reproductive risks are more strongly associated with the treatment of HPV-related diseases than with HPV infection itself. Preventive strategies—especially HPV vaccination—remain central to reducing HPV-related disease burden. Although HPV vaccines are not routinely recommended during pregnancy, evidence supports the safety of inadvertent exposure around conception or during gestation, while potential long-term benefits of vaccination regarding reproductive health require further study. Full article

(This article belongs to the Special Issue Role of Human Papillomavirus Vaccines in Cervical and Vulvo-Vaginal Diseases)

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16 pages, 802 KB

Open AccessReview

Towards HDV Elimination Through HBV Vaccination: Global Strategies, Challenges, and Policy Gaps

by Enkhtuul Batbold, Naranjargal Dashdorj, Fabien Zoulim and Birke Bartosch

Vaccines 2026, 14(2), 179; https://doi.org/10.3390/vaccines14020179 - 14 Feb 2026

Viewed by 821

Abstract

Persistent infection with hepatitis D virus (HDV), also known as hepatitis delta, is considered the most severe form of chronic viral hepatitis. HDV is a defective RNA virus that depends on hepatitis B virus (HBV) for propagation. Despite its global distribution, HDV stays [...] Read more.

Persistent infection with hepatitis D virus (HDV), also known as hepatitis delta, is considered the most severe form of chronic viral hepatitis. HDV is a defective RNA virus that depends on hepatitis B virus (HBV) for propagation. Despite its global distribution, HDV stays a neglected part of the viral hepatitis agenda, often overlooked in surveillance systems and public health policy. This oversight is particularly concerning given HDV’s aggressive clinical course, characterized by more rapid progression to cirrhosis, liver failure, and hepatocellular carcinoma (HCC) compared to HBV mono-infection. Mongolia has the highest incidence and mortality rates of HCC worldwide, with approximately 47% of cases estimated to be attributable to chronic HDV infection. Globally, an estimated 12–25 million people are co-infected with HBV and HDV, although the true prevalence is higher due to insufficient screening and incomplete data collection. Because HDV infection is entirely dependent on HBV, prevention of HBV infection through effective vaccination stands for an indirect yet highly effective strategy to curb HDV transmission. The World Health Organization (WHO), together with the global health community, has established ambitious targets to eliminate viral hepatitis as a public health threat by 2030. However, achieving HDV elimination remains particularly challenging due to limited diagnostic capacity, low awareness, and minimal inclusion of HDV in national hepatitis programs. This review explores the intersection of HDV and HBV, focusing on how expanded and optimized HBV vaccination coverage can serve as a cornerstone of global HDV prevention efforts. We examine epidemiological evidence, scientific rationale, policy developments, and key implementation challenges, with particular attention to high-burden settings such as Mongolia. Finally, we propose strategic recommendations to bridge policy and practice gaps in HDV elimination. Full article

(This article belongs to the Special Issue Chronic Viral Infections and Cancer: Openings for Vaccines and Cure)

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16 pages, 3113 KB

Open AccessArticle

Ameliorative Impacts of an Essential Oil Blend on Immune Function and Intestinal Health in Broilers Challenged with a High-Dose Coccidial Vaccine

by Hongjun Yang, Minmin Li, Chunxue Liu, Yifen Hung, Bo Shen, Shuaipeng Guo, Rui Xu, Tao Hu, Wenjing Geng, Gaiqin Wang and Junlong Zhao

Vaccines 2026, 14(2), 178; https://doi.org/10.3390/vaccines14020178 - 13 Feb 2026

Viewed by 644

Abstract

Background: The emergence of coccidial drug resistance has intensified the search for sustainable, residue-free solutions to control poultry coccidiosis. This challenge has positioned plant essential oils as promising candidates among the priority research areas. The study aimed to investigate the efficacy of essential [...] Read more.

Background: The emergence of coccidial drug resistance has intensified the search for sustainable, residue-free solutions to control poultry coccidiosis. This challenge has positioned plant essential oils as promising candidates among the priority research areas. The study aimed to investigate the efficacy of essential oils in improving immune function and intestinal health in white-feathered broilers challenged with a high-dose coccidial vaccine. Methods: A total of 480 one-day-old broilers were randomly assigned to five treatments: uninfected (CON), infected (EC), infected + 500 g/t narasin (AT), and infected + 200 or 400 g/t essential oil blend (EOB200 or EOB400). There were 6 replicates per treatment and 16 broilers per replicate. All infected treatments received a 30-fold coccidial vaccine on d 14. The CON group was administered an equal volume of sterile normal saline on d 14 of the experiment. One bird per replicate was sampled on d 22, and the remainder were raised until d 42. Results: Results showed that the challenge increased the fecal oocyst counts on d 21 and 28 and elevated intestinal lesion scores and serum interleukin-6 (IL-6) levels on d 21, while it decreased IL-10 levels on d 21 and reduced the villus height-to-crypt depth (V:C) ratio in the duodenum and jejunum (p < 0.05). Additionally, compared with the EC group, the AT, EOB200, and EOB400 groups reduced oocyst excretion and serum superoxide dismutase (SOD) (p < 0.05). The EOB200 group also showed the highest serum transforming growth factor-β (TGF-β) concentration, along with the lowest immunoglobulin G (IgG) level (p < 0.05). Moreover, within the infected groups, the EOB200 group exhibited the highest duodenal villus height and V:C ratio (p < 0.05). Conclusions: These findings indicated that the EOB200 and EOB400 groups alleviated intestinal damage caused by the coccidial vaccine with an efficacy comparable to that of antibiotics, and the EOB200 group exhibited a superior effect. The results confirm that the essential oil blend holds great application potential as an alternative to antibiotics. Full article

(This article belongs to the Section Veterinary Vaccines)

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24 pages, 1480 KB

Open AccessReview

Future Perspectives on the Application of Systems Biology and Generative Artificial Intelligence in the Design of Immunogenic Peptides for Vaccines

by José M. Pérez de la Lastra, Isidro Sobrino, Víctor M. Rodríguez Borges and José de la Fuente

Vaccines 2026, 14(2), 177; https://doi.org/10.3390/vaccines14020177 - 13 Feb 2026

Cited by 1 | Viewed by 971

Abstract

Peptide-based vaccines offer a modular and readily manufacturable platform for both prophylactic and therapeutic immunization. However, their broader translation has been constrained by the limited capacity to predict protective immunity directly from sequence-level features. Recent advances in systems vaccinology and high-throughput immune profiling [...] Read more.

Peptide-based vaccines offer a modular and readily manufacturable platform for both prophylactic and therapeutic immunization. However, their broader translation has been constrained by the limited capacity to predict protective immunity directly from sequence-level features. Recent advances in systems vaccinology and high-throughput immune profiling have substantially expanded the experimental evidence, while generative artificial intelligence now enables de novo design of peptide immunogens and multi-epitope antigens under precisely controlled constraints. This review approaches how these complementary developments are transforming peptide vaccine research, moving beyond classical reverse vaccinology and conventional epitope prediction toward integrated, data-driven design frameworks. We discuss key generative model architectures and conditioning strategies aligned with vaccine objectives, including approaches that account for structural presentation, antigen processing and population-level human leukocyte antigen (HLA) diversity. Central to this perspective is the requirement for rigorous experimental validation and for strengthening the computational–experimental feedback loop through iterative in vitro and in vivo testing informed by systems-level immune readouts. We highlight representative applications spanning infectious diseases, cancer immunotherapy and vector-borne vaccinology, and we outline major technical and translational challenges that must be addressed to enable robust real-world deployment. Finally, we propose future directions for precision peptide vaccinology, emphasizing standardized functional benchmarks, the development of richer curated datasets linking sequence space to immune outcomes, and the early incorporation of formulation and delivery constraints into generative design pipelines. Full article

(This article belongs to the Special Issue The Development of Peptide-Based Vaccines)

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13 pages, 1030 KB

Open AccessArticle

Pneumococcal Vaccination Uptake Among People with HIV Following the Implementation of an On-Site Vaccination Service in an Italian Specialist Out-Patient Clinic

by Anna Lisa Ridolfo, Maria Vittoria Cossu, Letizia Oreni, Cristina Gervasoni, Giacomo Casalini, Debora Visigalli, Catia Rosanna Borriello, Andrea Giacomelli, Andrea Gori and Spinello Antinori

Vaccines 2026, 14(2), 176; https://doi.org/10.3390/vaccines14020176 - 13 Feb 2026

Viewed by 499

Abstract

Background: People with HIV (PWH) face elevated risk of pneumococcal disease despite optimal antiretroviral therapy. In Italy, pneumococcal vaccination coverage in adults remains suboptimal. For PWH, access barriers may be amplified because adult vaccinations are primarily delivered in primary care, whereas HIV care [...] Read more.

Background: People with HIV (PWH) face elevated risk of pneumococcal disease despite optimal antiretroviral therapy. In Italy, pneumococcal vaccination coverage in adults remains suboptimal. For PWH, access barriers may be amplified because adult vaccinations are primarily delivered in primary care, whereas HIV care is mostly hospital-based. Methods: We conducted a retrospective, observational study at an HIV clinic in Milan, Italy, evaluating the impact of an on-site vaccination service implemented in January 2019. At baseline, 1854 PWH were in active follow-up; 135 (7.3%) had previously received pneumococcal vaccination. We assessed vaccination uptake (PCV13-PPSV23 sequential schedule or PCV20) among the remaining 1719 unvaccinated individuals through December 2023. A logistic regression analysis was used to identify factors associated with vaccine acceptance. Results: Over five years, 745/1719 individuals (43.3%) either initiated PCV13 + PPSV23 or received PCV20, representing a six-fold increase from baseline. Of 639 individuals receiving PCV13, 80.1% completed the sequence with PPSV23. Most vaccinations (80.8%) were administered on-site. In multivariable analysis, men who have sex with men showed higher uptake (aOR 1.56, 95% CI 1.25–1.95), while regular and irregular immigrants had significantly lower uptake (aOR 0.70 and 0.24, respectively) compared to Italian nationals. Conclusions: Integration of vaccination services into routine HIV care substantially improved pneumococcal vaccination uptake. However, with nearly half of eligible patients remaining unvaccinated, additional strategies are required to address vaccine hesitancy and inequities, particularly among immigrants, to achieve optimal pneumococcal coverage in PWH. Full article

(This article belongs to the Special Issue Vaccines for the Vulnerable Population)

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27 pages, 3189 KB

Open AccessArticle

Reaching Never- and Incompletely-Vaccinated Children with Routine Immunization: A Proof-of-Concept Activity Using Geo-Referenced Microplans in Two Health Zones in Maniema Province, Democratic Republic of the Congo

by Mary M. Alleman, Affaud Anais Tanon, Emmanuel Rukengwa, Kevin Tschirhart, Christ Lendo, Merveille Balepukayi, Grace Koko Cishugi, Eddy Balume Shaboya, Chuku Mburugu, Gloire Chasinga, Amy Louise Lang, Katherine Schwenk, Roger Widmer, Stéphane Vouillamoz, Jean Jacques Kanyaka Biduaya, Alain Magazani, John Kaozi, Generose Matunda Sumaili, Serge Sukani, Dolla Ngwanga Lapaba, Kimberly E. Bonner, Robert T. Perry, Jean Crispin Mukendi, Aimé Cikomola Mwana wa bene and Paul Lame Show full author list Hide full author list

Vaccines 2026, 14(2), 175; https://doi.org/10.3390/vaccines14020175 - 13 Feb 2026

Viewed by 743

Abstract

Background/Objectives: The Democratic Republic of the Congo (DRC) has a history of low coverage (<50%) with all first-year-of-life vaccines for children aged 12–23 months, resulting in frequent outbreaks of vaccine-preventable diseases. In response, the DRC’s Expanded Program on Immunization (EPI) is applying innovations [...] Read more.

Background/Objectives: The Democratic Republic of the Congo (DRC) has a history of low coverage (<50%) with all first-year-of-life vaccines for children aged 12–23 months, resulting in frequent outbreaks of vaccine-preventable diseases. In response, the DRC’s Expanded Program on Immunization (EPI) is applying innovations to improve vaccination coverage, including using geospatial data to inform vaccination planning (geo-referenced microplans). This report describes a proof of concept to geo-locate, by locality of residence, never-vaccinated children (NVC) or incompletely vaccinated children (IVC); use those data to prepare geo-referenced microplans for rounds of Periodic Intensification of Routine Immunization (PIRIs); and implement the PIRIs. Methods: In 2022, in Kindu and Kibombo Health Zones (HZs), Maniema Province, DRC, children aged 0–23 months were enumerated with inquiries about their vaccination status and reasons for non-vaccination by locality of residence. The enumeration was coupled with the collection of the localities’ geographic coordinates, facilitating the spatial illustration of estimated proportions of NVC by locality. Coordinates for HZ and health area (HA) landmarks and borders were also collected. We created maps that informed geo-referenced PIRI microplans, placing an emphasis on deploying vaccination teams to localities with high proportions of NVC, especially those in remote and riverine locations. To account for inclusion of children aged up to 59 months in the PIRIs, enumeration data were extrapolated to estimate the numbers of NVC and IVC in this wider age range. Volunteers mobilized communities for the PIRIs, HA staff vaccinated age-eligible children, and vaccination teams were geographically tracked. Results: In Kindu, 29,837 children aged 0–23 months were enumerated in 430 localities; among them, 38% were NVC and 6% IVC. In Kibombo, 9582 children aged 0–23 months were enumerated in 168 localities; among them, 50% were NVC and 16% IVC. In both HZs, reasons for never vaccination were primarily associated with knowledge- or belief-related factors, while reasons for incomplete vaccination were associated with access-related factors. Between HAs and localities, there was heterogeneity in the proportions of NVC and IVC and in the reasons for non-vaccination. The numbers of NVC and IVC aged 0–59 months were estimated at 28,220 and 4613 in Kindu and 12,038 and 3785 in Kibombo. Approximately 2000 health staff and community volunteers were engaged for implementation of each of the three PIRIs. The number of children vaccinated during the three PIRIs ranged from 15,500 to 26,500 and from 10,500 to 15,500 in Kindu and Kibombo, respectively. Data suggest that vaccinated children originated from >90% of localities identified during the cartography. Tracking data showed that vaccination teams visited localities with high proportions of NVC, including those that were remote and riverine. Conclusions: Geo-referenced microplanning with engagement of health staff and communities succeeded in vaccinating at least 40,000 children who were not routinely benefiting from health services in two HZs in the DRC; similar innovative strategies could be considered elsewhere. Applying new technologies to existing microplanning strategies can enhance their success. Full article

(This article belongs to the Special Issue The Role of Vaccination on Public Health and Epidemiology)

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29 pages, 880 KB

Open AccessArticle

Public Perceptions and Influencing Factors of Non-National Immunization Program (Non-NIP) Vaccines in Shanghai: A Population-Based Study

by Haifeng Ma, Yu Zhang, Danni Zhao, Hongmei Lu, Ping Yu, Jialei Fan, Qiangsong Wu, Wenjiang Zhong, Huiyong Shao, Xiaodong Sun, Zhuoying Huang and Linlin Wu

Vaccines 2026, 14(2), 174; https://doi.org/10.3390/vaccines14020174 - 13 Feb 2026

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Abstract

This study aimed to explore the cognitive levels and influencing factors of Shanghai residents regarding non-immunization program vaccines. A population-based study was conducted in Shanghai in 2024. Objective: To examine awareness levels and factors influencing perceptions of non-National Immunization Program (non-NIP) vaccines among [...] Read more.

This study aimed to explore the cognitive levels and influencing factors of Shanghai residents regarding non-immunization program vaccines. A population-based study was conducted in Shanghai in 2024. Objective: To examine awareness levels and factors influencing perceptions of non-National Immunization Program (non-NIP) vaccines among residents of Shanghai. Methods: A population cross-sectional survey was conducted in Shanghai from 20 October to 31 December 2024, using stratified random sampling. Five districts were selected, four communities per district were randomly chosen, and 35–40 residents per community were invited to complete a questionnaire. Data collected included sociodemographic characteristics, awareness of non-NIP vaccines, and potential influencing factors. Awareness and acceptance of non-NIP vaccines were measured using five-point Likert scales. On a 0–4 scale, where 0 = completely unaware/unsupportive and 4 = very aware/strongly supportive, respondents rated their level of understanding and endorsement of non-NIP vaccines. Descriptive analysis, the Kruskal–Wallis test, and ordinal logistic regression were used to assess awareness levels and their determinants. Results: Among the 753 respondents, 15.5% of respondents reported very high awareness, 18.7% reported fairly high awareness, 32.1% reported moderate awareness, 27.2% reported somewhat low awareness, and 6.5% reported complete unawareness. Acceptance levels were distributed as follows: 20.3% strongly in favour, 24.7% somewhat in favour, 45.9% neutral, 7.3% somewhat opposed, and 1.9% strongly opposed. Higher awareness was significantly associated with younger age, higher household living standard, receiving a recommendation from medical personnel, and participation in vaccine education programs (all p < 0.05). Acceptance was significantly influenced by age, residence type (urban community, town center, or rural), medical personnel recommendation, educational campaign participation, and perceived affordability of vaccine cost (all p < 0.05). Conclusions: Overall, Shanghai residents exhibited suboptimal awareness and acceptance of non-NIP vaccines, with a clear “high acceptance but low knowledge” phenomenon. To improve awareness, strategies should include strengthening healthcare providers’ recommendations and implementing systematic educational campaigns. To enhance acceptance, efforts should focus on disseminating positive, evidence-based information; reinforcing provider guidance; expanding outreach and education; and optimizing payment mechanisms to improve economic accessibility. Full article

(This article belongs to the Special Issue Vaccination and Public Health Strategy)

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26 pages, 649 KB

Open AccessReview

Challenges and Prospects in the Development of a Universal SARS-CoV-2 Vaccine

by Kacper Karczmarzyk and Małgorzata Kęsik-Brodacka

Vaccines 2026, 14(2), 173; https://doi.org/10.3390/vaccines14020173 - 13 Feb 2026

Viewed by 1101

Abstract

The development of a universal SARS-CoV-2 vaccine holds great promise for achieving broad and durable protection against existing and future coronavirus variants. The identification, selection, and rational redesign of conserved viral epitopes constitute the direct immunological foundation of universal SARS-CoV-2 vaccine development. The [...] Read more.

The development of a universal SARS-CoV-2 vaccine holds great promise for achieving broad and durable protection against existing and future coronavirus variants. The identification, selection, and rational redesign of conserved viral epitopes constitute the direct immunological foundation of universal SARS-CoV-2 vaccine development. The breadth and durability of protection are therefore primarily determined at the level of antigen and epitope design, whereas adjuvants, delivery platforms, and routes of administration serve as enabling and amplifying components rather than primary drivers of universality. Accordingly, this review discusses key determinants of universal vaccine design, including antigen selection, adjuvant utilization, and route of administration. The spike protein, particularly its receptor-binding domain, is a major antigenic target, but its high mutation rate challenges long-term vaccine efficacy. Strategies focusing on conserved epitopes in antigen designs show potential to elicit cross-neutralizing immune responses. Nanoparticle-based vaccines capable of presenting multiple homologous or heterologous antigens have demonstrated enhanced immunogenicity, broad protection in preclinical models and safety in clinical trials. The addition of next-generation adjuvants further amplifies humoral and cellular immunity beyond the capabilities of traditional aluminum-based adjuvants. Moreover, mucosal vaccine delivery may provide superior local protection at viral entry sites and limit transmission. Importantly, integrating these technological advances with epitope-centered antigen design and immunological data from vaccinated individuals will accelerate the identification of conserved epitopes and inform future vaccine design. A multidisciplinary approach combining optimized antigen engineering, novel adjuvant systems, and innovative delivery strategies is essential for the realization of a broadly protective universal SARS-CoV-2 vaccine. Full article

(This article belongs to the Special Issue Evaluation of Vaccine Efficacy, Safety and Immunogenicity Against Influenza, RSV and COVID-19)

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13 pages, 420 KB

Open AccessArticle

Feasibility and Safety of Autologous Dendritic Cell Vaccination Combined with Radio-Chemotherapy in Newly Diagnosed Glioblastoma: A Retrospective Single-Center Series

by Inés Esparragosa Vázquez, Ascensión López-Díaz de Cerio, Susana Inoges, Javier Aristu, Pablo Domínguez, Reyes García-Eulate, Marta Calvo-Imirizaldu, Javier Arbizu, María E. Rodríguez-Ruiz, Pablo Irimia, Marta M. Alonso, Felipe Prósper, Ricardo Díez-Valle and Jaime Gállego Pérez-Larraya

Vaccines 2026, 14(2), 172; https://doi.org/10.3390/vaccines14020172 - 12 Feb 2026

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Abstract

Background: The prognosis of glioblastoma (GBM) patients remains poor. Dendritic cell (DC) vaccination has been investigated as an immunotherapy option, mainly in early-phase clinical studies. Herein, we report the feasibility, safety, and descriptive clinical and radiological outcomes of a retrospective series of newly [...] Read more.

Background: The prognosis of glioblastoma (GBM) patients remains poor. Dendritic cell (DC) vaccination has been investigated as an immunotherapy option, mainly in early-phase clinical studies. Herein, we report the feasibility, safety, and descriptive clinical and radiological outcomes of a retrospective series of newly diagnosed GBM patients treated with standard radio-chemotherapy and autologous DC vaccination as compassionate use. Methods: We retrospectively reviewed the medical and radiological records of patients with newly diagnosed GBM who received autologous tumor lysate–pulsed DC vaccination in addition to standard-of-care treatment at a tertiary academic center between 2009 and 2017. Clinical data, treatment characteristics, adverse events, survival outcomes, and radiological responses were collected and analyzed descriptively. Results: Twenty-four patients were included. All patients underwent surgical resection and were further treated with autologous tumor lysate–DC vaccination and standard radio-chemotherapy. Histology of GBM was confirmed in all patients. The first vaccine was administered in 75% of patients after a median of 21 days (range: 6–30 days) following surgery and prior to radiotherapy initiation. DC vaccination was continued following radiotherapy at specific time points, with no observed significant adverse events. Median OS was 21.1 months (95% CI, 27.9–75.0 months), and median PFS was 10.3 months (95% CI, 15.6–26.6 months). Presence of O6-methylguanine DNA methyltransferase (MGMT) promoter methylation was associated with longer survival and higher 12-month PFS rates, consistent with its established prognostic value. Radiological responses were retrospectively assessed according to RANO and RANO 2.0 criteria. Conclusions: In this retrospective single-center series, autologous DC vaccination administered as compassionate use in combination with standard radio-chemotherapy was feasible and safe in routine clinical practice. Survival and radiological outcomes are reported descriptively and should be interpreted with caution given the absence of a control cohort. These findings support further prospective controlled studies to properly assess the clinical role of DC vaccination in newly diagnosed GBM. Full article

(This article belongs to the Special Issue The Era of Vaccines: Advancing Tumor Immunology and Immunotherapy)

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15 pages, 266 KB

Open AccessArticle

Evaluating a Tailored Quality Improvement Intervention to Improve Vaccination Coverage in Sydney Residential Aged Care Facilities

by Courtney McGregor, Lauren Tillman, Lisa Maude, Karen Chee, Caitlin Swift, Leigh McIndoe, Mark Ferson, Brendan Goodger, Kira Wright and Vicky Sheppeard

Vaccines 2026, 14(2), 171; https://doi.org/10.3390/vaccines14020171 - 12 Feb 2026

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Abstract

Background/Objectives: Aged care residents are highly vulnerable to vaccine-preventable diseases. Despite recommendations and funding under Australian programs, vaccination rates among residents for COVID-19, influenza, pneumococcal and shingles remain sub-optimal. The aim of this work was to assess if tailored quality improvement interventions would [...] Read more.

Background/Objectives: Aged care residents are highly vulnerable to vaccine-preventable diseases. Despite recommendations and funding under Australian programs, vaccination rates among residents for COVID-19, influenza, pneumococcal and shingles remain sub-optimal. The aim of this work was to assess if tailored quality improvement interventions would improve vaccination coverage in aged care residents. Methods: This was a quality improvement initiative evaluated using a quasi-experimental pre–post design. Building on previously identified barriers and enablers, a package of interventions and resources was developed to support consent processes, vaccination planning, and tracking. Pre- and post-intervention vaccination coverage was assessed using resident lists from participating aged care facilities and data extracted from the Australian Immunisation Register (AIR) at two time points, 14 months apart. A process evaluation survey was distributed to RACF staff. Results: Of the 6964 residents listed, 5153 (74%) remained registered in AIR when data was extracted post-intervention. Shingles showed the greatest improvement in absolute difference (+23.4%), followed by pneumococcal (+14.2%) and influenza (+10.9%), despite a high baseline of 68.5%. COVID-19 coverage declined by 7.4% when applying a 6-month reporting interval. Twenty-five staff completed the process evaluation survey; 45% of respondents identified discrepancies between AIR data and internal records, indicating underreporting by external providers. Interventions including the consent template and vaccination tracker were reported as useful and were used to support local vaccination. Conclusions: This quality improvement initiative improved coverage for three of the four recommended and funded vaccines for RACF residents and demonstrated the value of tailored interventions informed by consumer and provider feedback. The approach potentially offers a scalable model for improving vaccination rates in aged care across Australia. Full article

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

15 pages, 2200 KB

Open AccessArticle

Potency of a Live Attenuated GPE⁻ Vaccine Against an Antigenically Distinct Classical Swine Fever Virus Strain in Japan

by Tatsuya Nishi, Emiko Ito, Miyabi Nishimura, Tomoko Kato, Mizuki Watanabe, Kentaro Masujin, Yoshitaka Imaizumi and Katsuhiko Fukai

Vaccines 2026, 14(2), 170; https://doi.org/10.3390/vaccines14020170 - 12 Feb 2026

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Abstract

Background: Highly potent vaccines are essential for the effective control of classical swine fever (CSF). Since CSF re-emerged in 2018 in Japan, the live CSF virus (CSFV) vaccine—a guinea pig exaltation of Newcastle disease virus-negative strain vaccine (GPE⁻, genotype 1.1)—has [...] Read more.

Background: Highly potent vaccines are essential for the effective control of classical swine fever (CSF). Since CSF re-emerged in 2018 in Japan, the live CSF virus (CSFV) vaccine—a guinea pig exaltation of Newcastle disease virus-negative strain vaccine (GPE⁻, genotype 1.1)—has been applied to domestic pigs, contributing to a reduction in outbreaks. Meanwhile, the persistence and continued expansion of CSFV in wild boar populations have raised concerns regarding potential antigenic divergence. Methods: We systematically evaluated the neutralizing reactivity of sera from GPE⁻-vaccinated pigs against CSFV strains (genotype 2.1) recently circulating in Japan against identified a representative strain that showed markedly reduced neutralization. We directly assessed the protective efficacy of the GPE⁻ vaccine against this strain in a controlled challenge experiment. At 4 weeks post-vaccination, both vaccinated and unvaccinated pigs were orally challenged with the representative Japanese strain and monitored for 3 weeks thereafter. Results: Among the Japanese CSFV strains, the JPN/SM/WB/2022 isolate exhibited markedly reduced neutralizing reactivity—over 32-fold lower than that against the vaccine strain—when tested with GPE⁻ vaccine-induced antisera. In the experimental infection in pigs, unvaccinated pigs exhibited typical clinical signs of CSF and viremia, and two pigs reached the humane endpoint. In contrast, none of the vaccinated pigs showed any clinical signs of infection. Robust humoral and cellular immune responses were induced in vaccinated pigs, which may correlate with the observed complete protection. Conclusions: The GPE^– live vaccine provides protective immunity against an antigenically distinct strain, prevents disease, and limits viral spread in domestic pigs. Full article

(This article belongs to the Special Issue Classical Swine Fever Virus Vaccines)

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19 pages, 4538 KB

Open AccessArticle

Rational Combination of Dominant and Subdominant Antigens with Nanoadjuvant Elicits Durable Immunity Against Staphylococcus aureus

by Zhuoyue Shi, Jiayue Xi, Minxuan Cui, Zhuo Wan, Yufei Hou, Zhengjun Ma, Nan Sun, Yupu Zhu, Muqiong Li, Dong Wang, Xin He, Qian Yang, Chaojun Song and Li Fan

Vaccines 2026, 14(2), 169; https://doi.org/10.3390/vaccines14020169 - 12 Feb 2026

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Abstract

Objectives: In response to the challenge that Staphylococcus aureus (S. aureus) vaccines fail to induce durable protective immunity, this study aims to develop a novel antigen-adjuvant co-design strategy. Specifically, we rationally combined the immunodominant toxin antigen LukS-PV with the immunologically subdominant [...] Read more.

Objectives: In response to the challenge that Staphylococcus aureus (S. aureus) vaccines fail to induce durable protective immunity, this study aims to develop a novel antigen-adjuvant co-design strategy. Specifically, we rationally combined the immunodominant toxin antigen LukS-PV with the immunologically subdominant adhesin antigen ClfA, co-delivered via the PLGA-PEG nanoadjuvant system, to elicit synergistic, durable, and balanced humoral and cellular immune responses. Methods: Firstly, recombinant antigens LukS-PV and ClfA were individually covalently conjugated to PLGA-PEG 25% nanoparticles (25% NPs) using EDC/NHS chemical coupling to construct a combined nanovaccine, followed by systemic safety verification in a mouse model. Subsequently, specific antibody titers were detected by ELISA, and the secretion levels of IL-4, IFN-γ, and IL-17A were measured by ELISPOT assay to comprehensively evaluate the humoral and cellular immune responses induced by the vaccine. Finally, the protective efficacy of the vaccine was assessed through acute and long-term (up to 180 days) lethal challenge experiments, thereby verifying the effectiveness of this co-design strategy based on rational antigen selection. Results: The combined vaccine group (25% NPs-rClfA + 25% NPs-rLukS-PV) not only elicited high levels of specific antibodies but, more importantly, induced robust cellular immune responses dominated by Th1 and Th17 cells. Challenge experiments confirmed that the protective efficacy of the combined vaccine was significantly superior to that of any single-antigen vaccine and provided complete protection for up to 180 days. Crucially, the same antigen combination formulated with a traditional aluminum adjuvant failed to confer this durable protection, underscoring the essential role of adjuvant synergy. Conclusions: This study demonstrates that rational combination of immunodominant and subdominant antigens with a compatible nanoadjuvant induces synergistic and durable immunity against S. aureus. This co-design strategy addresses key limitations of previous vaccines and provides a promising foundation for future clinical development. Full article

(This article belongs to the Special Issue Advances in Vaccine Adjuvants)

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7 pages, 168 KB

Open AccessEditorial

Immune Response to COVID-19 Vaccines: Updates in a Fast-Moving Scenario

by Federico De Marco

Vaccines 2026, 14(2), 168; https://doi.org/10.3390/vaccines14020168 - 12 Feb 2026

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Abstract

The prompt and extensive use of COVID-19 vaccines has dramatically reduced both cases and casualties, but it has also underscored a number of critical issues that need to be addressed for their full exploitation at global level. This Special Issue was launched to [...] Read more.

The prompt and extensive use of COVID-19 vaccines has dramatically reduced both cases and casualties, but it has also underscored a number of critical issues that need to be addressed for their full exploitation at global level. This Special Issue was launched to gather fresh data to improve the way we use vaccines that are currently available to contribute to the design and the development of new ones and to elucidate social, ethical and psychological concerns that might hamper vaccine acceptance and use. It includes 15 articles six of which address, under various aspects, the level and durability of protective immunity; five deal with the highly debated field of vaccine use, efficacy and safety, in persons with an impaired/dysregulated immune system; one paper reports on adjuvants’ role in immune stimulation; one on the interference of natural adenovirus immunity with DNA vaccine response; one is a review on the cellular mechanisms of vaccine-dependent myocarditis; and one explores social attitudes to vaccines in different ethnic groups during early phases of the pandemic. Far from being complete and exhaustive, this Special Issue provides the reader with fresh insights into several critical questions raised by or connected to the advent of COVID-19 vaccines. This introductory article provides an overview of their contribution, while offering a quick glance at the current state of the art. Full article

(This article belongs to the Special Issue Understanding Immune Responses to COVID-19 Vaccines)

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Vaccines, Volume 14, Issue 2 (February 2026) – 88 articles

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