Vaccines

13 pages, 2870 KB

Open AccessArticle

A Chemically Induced Vibrio harveyi Bacterial Ghost Vaccine Confers Enhanced Protection in Turbot (Scophthalmus maximus)

by Haixiang Lv, Jianye Yang, Ruofan Yu, Qin Liu and Xiaohong Liu

Vaccines 2026, 14(1), 109; https://doi.org/10.3390/vaccines14010109 - 22 Jan 2026

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Abstract

Background: Vibrio harveyi is a major bacterial pathogen threatening turbot aquaculture, necessitating the development of more effective vaccines. Bacterial ghosts (BGs), which are empty bacterial envelopes with preserved surface antigens, offer a promising alternative to traditional formaldehyde-killed vaccines that often suffer from reduced [...] Read more.

Background: Vibrio harveyi is a major bacterial pathogen threatening turbot aquaculture, necessitating the development of more effective vaccines. Bacterial ghosts (BGs), which are empty bacterial envelopes with preserved surface antigens, offer a promising alternative to traditional formaldehyde-killed vaccines that often suffer from reduced immunogenicity. Methods: We developed an optimized BGs vaccine for V. harveyi by combining the nonionic surfactant NP-40 with sodium hydroxide (NaOH). This NP-40/NaOH combination demonstrated a synergistic lytic effect, halving the minimum inhibitory concentration of NaOH required for complete inactivation. Results: The resulting BGs exhibited intact cellular morphology with transmembrane pores, efficient removal of cytoplasmic contents, and significantly better preservation of lipopolysaccharide structure compared to NaOH-alone treatment. Vaccination trials in turbot demonstrated that the NP-40/NaOH BGs provided the highest relative percent survival (RPS = 58.8%) upon challenge, outperforming both NaOH-alone BGs (RPS = 55.0%) and a traditional formaldehyde-killed vaccine (RPS = 34.8%). The superior protection was correlated with the induction of a more robust and sustained immune response, characterized by significantly higher levels of specific IgM antibodies, elevated lysozyme activity, and increased total serum protein. Conclusions: This study establishes the NP-40/NaOH protocol as an effective strategy for producing high-quality BGs with enhanced immunogenicity, presenting a potent vaccine candidate for controlling vibriosis in aquaculture. Full article

(This article belongs to the Special Issue Advances in Aquatic Animal Immunology and Vaccine Development for Disease Prevention)

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11 pages, 884 KB

Open AccessReview

Shifting Perspective in Influenza Vaccines Efficacy: How Risk Difference Shows an Alternative View of the Comparative Efficacy Profile of Newer and Enhanced Influenza Vaccines Compared to Standard, Egg-Based Vaccines

by Laura Colombo, Abraham Palache and Sanjay Hadigal

Vaccines 2026, 14(1), 108; https://doi.org/10.3390/vaccines14010108 - 22 Jan 2026

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Abstract

Annual influenza vaccination remains critical for mitigating severe illness and reducing healthcare strain, particularly among high-risk populations. Despite advancements in vaccine platforms, the comparative efficacy of novel vaccines—such as high-dose (HD-IIV), recombinant (rIV), cell-based (cIV), and adjuvanted (aIV) influenza vaccines—versus standard-dose non-adjuvanted (SD-IIV) [...] Read more.

Annual influenza vaccination remains critical for mitigating severe illness and reducing healthcare strain, particularly among high-risk populations. Despite advancements in vaccine platforms, the comparative efficacy of novel vaccines—such as high-dose (HD-IIV), recombinant (rIV), cell-based (cIV), and adjuvanted (aIV) influenza vaccines—versus standard-dose non-adjuvanted (SD-IIV) vaccines remains a public health concern. Traditional Relative Vaccine Efficacy (rVE) metrics, though robust, may overestimate population-level benefits. This short communication explores alternative comparative efficacy measures: risk difference (ΔRD) and number needed to vaccinate (ΔNNV). Analysis of data derived from randomized controlled trials (RCTs), or robust pragmatic trials, shows that while rVE values for newer vaccines often indicate superior efficacy, ΔRD and ΔNNV highlight the limits in incremental protection at the population level, with ΔRD generally below 10 cases per 1000 vaccinated. These findings underline the sustained relevance of SD-IIV in immunization programs and emphasize the need for broader vaccine coverage to highlight the benefits of vaccination and enhance population health outcomes. Full article

(This article belongs to the Special Issue The Recent Development of Influenza Vaccine: 2nd Edition)

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15 pages, 1991 KB

Open AccessArticle

Development of an mRNA Vaccine for Tick-Borne Encephalitis: Selection of a Prototype Virus Strain

by Maria A. Nikiforova, Vladimir A. Gushchin, Denis A. Kleymenov, Anastasia M. Kocherzhenko, Evgeniia N. Bykonia, Elena P. Mazunina, Sofia R. Kozlova, Leonid I. Russu, Nadezhda A. Kuznetsova, Elena V. Shidlovskaya, Elizaveta V. Marchuk, Evgeny V. Usachev, Olga V. Usacheva, Dmitry V. Shcheblyakov, Irina V. Kozlova, Sergei E. Tkachev, Andrei A. Pochtovyi, Vladimir I. Zlobin, Denis Y. Logunov and Alexander L. Gintsburg

Vaccines 2026, 14(1), 107; https://doi.org/10.3390/vaccines14010107 - 21 Jan 2026

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Abstract

Background/Objectives: While tick-borne encephalitis virus (TBEV) is genetically relatively conserved, the significant antigenic divergence between its main circulating subtypes hinders the development of broadly effective antiviral treatments and vaccines. Current inactivated TBEV vaccines offer limited cross-protection against heterologous strains, as evidenced by [...] Read more.

Background/Objectives: While tick-borne encephalitis virus (TBEV) is genetically relatively conserved, the significant antigenic divergence between its main circulating subtypes hinders the development of broadly effective antiviral treatments and vaccines. Current inactivated TBEV vaccines offer limited cross-protection against heterologous strains, as evidenced by cases among vaccinated individuals in endemic regions. The aim of this study was to design a candidate mRNA vaccine and evaluate the breadth of protective immunity it elicits. Methods: Ten candidate mRNA-PrM/E-LNP vaccines were comparatively evaluated for immunogenicity and protective efficacy in BALB/c mice. Immunogenicity was assessed by measuring antigen-specific IgG titers via ELISA and neutralizing antibody titers against a panel of TBEV strains using a virus-neutralization test. Protective efficiency was determined in a lethal challenge model, where immunized mice were challenged with one of seven distinct TBEV strains. Results: Vaccination with all tested mRNA-PrM/E-LNP candidates conferred 100% survival in mice following a lethal challenge with each of the seven TBEV strains (100 LD₅₀). The construct mRNA-PrM/E—Krasny Yar-8 demonstrated the highest immunogenicity, inducing antigen-specific antibodies with a geometric mean titer (GMT) of 1:6625, as well as the broadest virus-neutralizing activity against both homologous and heterologous TBEV strains in vitro. Conclusions: The mRNA platform represents a promising strategy for developing TBEV vaccines, demonstrating high immunogenicity and cross-protective efficacy against diverse viral strains. Full article

(This article belongs to the Special Issue Feature Papers of DNA and mRNA Vaccines)

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15 pages, 2088 KB

Open AccessArticle

Preparation and Efficacy Evaluation of Heat-Resistant Freeze-Dried Live-Attenuated Vaccine Formulation of Micropterus salmoides Rhabdovirus

by Hongru Liang, Guangwei Hu, Xia Luo, Qiang Lin, Xiaozhe Fu, Yinjie Niu, Baofu Ma, Wenwen Xiao, Zhengwei Cui and Ningqiu Li

Vaccines 2026, 14(1), 106; https://doi.org/10.3390/vaccines14010106 - 21 Jan 2026

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Abstract

Background/Objectives: An attenuated strain of Micropterus salmoides rhabdovirus (MSRV) 0509 with good immunogenicity has been isolated, showing potential as a candidate for live vaccine development. Methods: To improve the shelf life of attenuated strain of MSRV0509, the virus was formulated using three distinct [...] Read more.

Background/Objectives: An attenuated strain of Micropterus salmoides rhabdovirus (MSRV) 0509 with good immunogenicity has been isolated, showing potential as a candidate for live vaccine development. Methods: To improve the shelf life of attenuated strain of MSRV0509, the virus was formulated using three distinct single-protectant formulations and twelve thermostable protective agent formulations (designated T1–T12). Following lyophilization, the thermostability of each formulation was evaluated. Results: Results indicated that formulations T1, T9, and T10 maintained stable viral titers after storage at 25 °C and 37 °C. Moreover, these formulations retained high viral viability after 12 months at 4 °C, with a titer reduction of less than 0.5 log₁₀. Immunological analyses revealed that the freeze-dried MSRV vaccine elicited both humoral and immune factors responses in largemouth bass. Immersion immunization provided effective protection, yielding a survival rate exceeding 80%. Freeze-dried vaccines maintained their immunogenicity (i.e., the ability to induce antibodies) following 12 months of storage at 4 °C. Additionally, expression of IFN-γ and IL-12 was significantly upregulated in fish post-vaccination. Conclusions: In conclusion, the lyophilized MSRV vaccine developed in this study not only exhibits improved thermostability and extended shelf life, but also effectively preserves its immunogenic properties, supporting its potential for practical aquaculture applications. Full article

(This article belongs to the Section Veterinary Vaccines)

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18 pages, 691 KB

Open AccessReview

Vaccination Against Respiratory Infections in Adults with Cancer: A Concise Guide for Clinicians

by Kay Choong See

Vaccines 2026, 14(1), 105; https://doi.org/10.3390/vaccines14010105 - 21 Jan 2026

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Abstract

Global cancer incidence reached 20 million new cases across 185 countries in 2022, with approximately 10 million cancer-related deaths annually. Among adults with solid tumors and hematological malignancies, infections are a major contributor to morbidity and mortality, with respiratory infections playing a particularly [...] Read more.

Global cancer incidence reached 20 million new cases across 185 countries in 2022, with approximately 10 million cancer-related deaths annually. Among adults with solid tumors and hematological malignancies, infections are a major contributor to morbidity and mortality, with respiratory infections playing a particularly significant role. These infections not only reduce life expectancy but can also delay cancer therapy, negatively affect treatment outcomes, and increase healthcare costs. In recent years, the burden of respiratory infections in this population has been driven by influenza virus, SARS-CoV-2, respiratory syncytial virus, Streptococcus pneumoniae, and Bordetella pertussis. Effective vaccines are available for all these pathogens and are recommended for adults with cancer, yet vaccination uptake remains suboptimal despite their heightened vulnerability. This review provides practical guidance for healthcare professionals on vaccinating adults with cancer against respiratory infections, summarizing key information to help clinicians address vaccination-related complacency, confidence, and convenience. Evidence from studies in both the general population and cancer patients consistently shows that vaccination benefits outweigh potential risks, with adverse event rates comparable to those seen in individuals without cancer. Early vaccination is encouraged, as there is limited justification for delaying immunization even when immune responses may be reduced. Vaccine dosing aligns with recommendations for the general population, with important exceptions. Live attenuated vaccines should be avoided because of the risk of replication and disease in immunocompromised patients, and selected groups may require booster doses to achieve adequate protection. Notably, cancer immunotherapy does not appear to impair vaccine-induced immune responses. Full article

(This article belongs to the Special Issue Challenges to Developing New Vaccines and Improving Existing Platforms)

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29 pages, 1055 KB

Open AccessReview

Hidden Targets in Cancer Immunotherapy: The Potential of “Dark Matter” Neoantigens

by Francois Xavier Rwandamuriye, Alec J. Redwood, Jenette Creaney and Bruce W. S. Robinson

Vaccines 2026, 14(1), 104; https://doi.org/10.3390/vaccines14010104 - 21 Jan 2026

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Abstract

The development of cancer immunotherapies has transformed cancer treatment paradigms, yet durable and tumour-specific responses remain elusive for many patients. Neoantigens, immunogenic peptides arising from tumour-specific genomic alterations, have emerged as promising cancer vaccine targets. Early-phase clinical trials using different vaccine platforms, including [...] Read more.

The development of cancer immunotherapies has transformed cancer treatment paradigms, yet durable and tumour-specific responses remain elusive for many patients. Neoantigens, immunogenic peptides arising from tumour-specific genomic alterations, have emerged as promising cancer vaccine targets. Early-phase clinical trials using different vaccine platforms, including mRNA, peptide, DNA, and viral vector-based personalised cancer vaccines, have demonstrated the feasibility of targeting neoantigens, with early signals of prolonged survival in some patients. Most current vaccine strategies focus on canonical neoantigens, typically derived from exonic single-nucleotide variants (SNVs) and small insertions/deletions (INDELs), yet this represents only a fraction of the potential neoantigen repertoire. Evidence now shows that non-canonical neoantigens, arising mostly from alternative splicing, intron retention, translation of non-coding RNAs, gene fusions, and retroelement activation, broaden the antigenic landscape, with the potential for increasing tumour specificity and immunogenicity. In this review, we explore the biology of non-canonical neoantigens, the technological advances that now enable their systematic detection, and their potential to inform next-generation personalised cancer vaccines. Full article

(This article belongs to the Special Issue Tumor Vaccines: Current Processes, Prevailing Challenges and Future Perspectives)

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17 pages, 4217 KB

Open AccessArticle

Elicitation of Protective Immune Responses Against Influenza Virus Following Intranasal Delivery of Fluzone or Flublok Vaccines

by Naoko Uno, Matthew H. Thomas, Camila Caetano and Ted M. Ross

Vaccines 2026, 14(1), 103; https://doi.org/10.3390/vaccines14010103 - 21 Jan 2026

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Abstract

Background/Objectives: While new vaccines are in development; one strategy to increase influenza vaccine coverage is to repurpose current influenza vaccines for intranasal delivery. Methods: To address this goal; mice were vaccinated intranasally with either a split inactivated virus vaccine (Fluzone) or a recombinant [...] Read more.

Background/Objectives: While new vaccines are in development; one strategy to increase influenza vaccine coverage is to repurpose current influenza vaccines for intranasal delivery. Methods: To address this goal; mice were vaccinated intranasally with either a split inactivated virus vaccine (Fluzone) or a recombinant HA vaccine (Flublok) at one of two doses (1 μg high dose or 0.1 μg low dose). Both vaccines were adjuvanted with either a STING agonist; c-di-AMP (CDA); or a combination of a synthetic toll-like receptor (TLR) 4 and TLR7/8 agonist (TRAC478). Results: Mice vaccinated with either vaccine plus adjuvant had higher hemagglutination-inhibition titers than mice administered unadjuvanted vaccines. Mice vaccinated with either vaccine plus CDA had on average higher numbers of H3 and influenza B hemagglutinin (HA)-specific antibody-secreting cells (ASCs); whereas mice vaccinated with vaccine plus TRAC478 had on average higher number of H1 HA-specific ASCs. All vaccinated mice challenged with the H1N1 influenza virus were protected against both morbidity and mortality with no detectable virus in their lungs. Mice challenged with the H3N2 influenza virus all lost weight over the first 5 days of infection. Adding TRAC478 with either a high or low dose vaccine resulted in 80–100% survival following challenge. Almost all mice vaccinated with Flublok plus CDA died from H3N2 influenza virus challenged with ~2 logs higher viral lung titers than mice administered Flublok only or Flublok plus TRAC478. Conclusions: Overall; Fluzone and Flublok can effectively be used for intranasal vaccination. Full article

(This article belongs to the Special Issue Immunity to Influenza Viruses and Vaccines)

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12 pages, 651 KB

Open AccessArticle

Real-World Effectiveness of Seasonal Influenza Vaccines During the 2024–2025 Season: Subgroup Analyses by Virus Subtype, Time Since Vaccination, and Diagnostic Method

by Yu Jung Choi, Jungmin Lee, Joon Young Song, Seong-Heon Wie, Jacob Lee, Jin-Soo Lee, Hye Won Jeong, Joong Sik Eom, Jang Wook Sohn, Young Kyung Yoon, Won Suk Choi, Eliel Nham, Jin Gu Yoon, Ji Yun Noh, Man-Seong Park and Hee Jin Cheong

Vaccines 2026, 14(1), 102; https://doi.org/10.3390/vaccines14010102 - 21 Jan 2026

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Abstract

Background/Objectives: Despite high vaccination coverage, influenza remains a public health concern in South Korea, particularly in older adults. Continuous evaluation of vaccine effectiveness (VE) is essential to optimize immunization strategies. Methods: This study evaluated seasonal influenza VE for preventing laboratory-confirmed influenza [...] Read more.

Background/Objectives: Despite high vaccination coverage, influenza remains a public health concern in South Korea, particularly in older adults. Continuous evaluation of vaccine effectiveness (VE) is essential to optimize immunization strategies. Methods: This study evaluated seasonal influenza VE for preventing laboratory-confirmed influenza using a test-negative design through a hospital-based influenza surveillance system in South Korea from 1 November 2024, to 30 April 2025. Demographic and clinical information was collected through questionnaire surveys and electronic medical records. Influenza was diagnosed using rapid antigen tests (RATs) and reverse transcription polymerase chain reaction (RT-qPCR), and vaccine effectiveness was analyzed using multivariable logistic regression. Results: In total, 3954 participants were included, with 1977 influenza-positive cases and 1977 test-negative controls. Influenza A and B accounted for 93.1% and 7.0% of cases, respectively. The adjusted overall VE was 20.4% (95% confidence interval [CI], 8.2–30.9; p = 0.002). VE was higher in adults aged 50–64 years (46.8%) than in those aged ≥65 years (18.8%). VE was 19.9% against influenza A and 45.7% against A/H3N2. VE was higher among individuals tested using RT-qPCR than among those tested using RATs (21.5% vs. 15.7%), and was also greater during the early period than during the late period (20.5% vs. 11.4%). Vaccination did not reduce influenza-associated hospitalization risk (VE, 17.3%; 95% CI, −9.3 to 37.4). A significant reduction in hospitalization risk was observed in adults aged 50–64 years (VE, 46.8%), with no significant benefit in those aged ≥65 years. Conclusions: The 2024–2025 seasonal influenza vaccine provided moderate protection against laboratory-confirmed influenza in adults, with higher effectiveness in those aged 50–64 years. Full article

(This article belongs to the Section Influenza Virus Vaccines)

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18 pages, 854 KB

Open AccessArticle

HPV and HIV Among Youth: Exploring the Role of Knowledge, Risk Perception, and Attitude to Vaccination in Prevention Strategies

by Silvia Cocchio, Andrea Cozza, Matilde Obici, Elisabetta Conte, Claudia Cozzolino Cangiano, Nicoletta Parise, Patrizia Furlan and Vincenzo Baldo

Vaccines 2026, 14(1), 101; https://doi.org/10.3390/vaccines14010101 - 21 Jan 2026

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Abstract

Background: Sexually transmitted infections (STIs) represent a significant public health problem due to their impact. Knowledge about them, perceptions of the risk of contracting them, and adherence to prevention strategies such as HPV vaccination are, at various levels, key factors in preventing [...] Read more.

Background: Sexually transmitted infections (STIs) represent a significant public health problem due to their impact. Knowledge about them, perceptions of the risk of contracting them, and adherence to prevention strategies such as HPV vaccination are, at various levels, key factors in preventing the spread of STIs. The study therefore aimed to investigate and evaluate, in a group of young Italians, the level of knowledge, perception of risk and propensity to adhere to preventive strategies, including vaccination against papillomavirus. Methods: A cross-sectional study was conducted by administering a questionnaire to young people aged between 16 and 30, residing in four macro-geographical areas, collecting socio-demographic, behavioral and knowledge data. Levels of knowledge about STIs and HPV were classified into four categories (low, medium without awareness, medium with awareness, high). Risk perception was assessed on a scale of 1 to 10. Results: A total of 2576 questionnaires were collected, revealing that general knowledge about STIs is limited: only 12.5% of participants demonstrated a high level of knowledge, while 27.1% demonstrated a low level; with regard to HPV, 41.3% of the sample demonstrated a low level of knowledge. The perception of the risk of contracting HIV and HPV was low in most subjects (average score of approximately 2.9 out of 10), with no significant differences related to levels of knowledge about HPV. Potential adherence to HPV vaccination was high (83.0% considered vaccination useful), but among unvaccinated subjects, almost half expressed concerns about vaccination, related to poor knowledge and mistrust of vaccines in general. Factors associated with a higher frequency of self-reported STIs included older age, transgender identity, non-heterosexual orientation, and risky sexual behavior. Conclusions: The results emerging from the study highlight the urgent need to strengthen educational and preventive interventions aimed at young people. Raising awareness of the risk of contracting STIs and the importance of vaccination are key targets for health promotion interventions. Full article

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

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3 pages, 133 KB

Open AccessEditorial

Closing Editorial—Special Issue on Veterinary Vaccines and Host Immune Responses

by Ayumi Matsuyama-Kato and Mohamed Faizal Abdul-Careem

Vaccines 2026, 14(1), 99; https://doi.org/10.3390/vaccines14010099 - 20 Jan 2026

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Abstract

As this Special Issue concludes, we are delighted to highlight the diversity, depth, and translational potential of the assembled contributions [...] Full article

(This article belongs to the Special Issue Veterinary Vaccines and Host Immune Responses)

11 pages, 1442 KB

Open AccessArticle

The Role of MASP1, MASP2, and Mannose-Binding Lectin in the Immune Response to Hepatitis B Vaccination in Infants

by Ayşe Esra Tapcı, İsmail Bulut, Serçin Taşar, Zeynep Kallimci, Kezban Çavdar Yetkin, Meliha Sevim, Oğuzhan Serin, Medine Ayşin Taşar, Mehmet Şenes and Bülent Alioğlu

Vaccines 2026, 14(1), 98; https://doi.org/10.3390/vaccines14010098 - 20 Jan 2026

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Abstract

Background: Hepatitis B vaccination is the most effective strategy for preventing chronic hepatitis B virus (HBV) infection; however, interindividual variability in vaccine-induced antibody responses remains a significant challenge in the field. Innate immune components, particularly lectin complement pathway proteins such as mannose-binding lectin [...] Read more.

Background: Hepatitis B vaccination is the most effective strategy for preventing chronic hepatitis B virus (HBV) infection; however, interindividual variability in vaccine-induced antibody responses remains a significant challenge in the field. Innate immune components, particularly lectin complement pathway proteins such as mannose-binding lectin (MBL), mannose-associated serine protease 1 (MASP-1), and mannose-associated serine protease 2 (MASP-2), may contribute to this variability in outcomes. This study aimed to evaluate the association between serum MBL, MASP-1, and MASP-2 levels, birth weight, and humoral response to hepatitis B vaccination in infants. Methods: This single-center prospective observational study included 37 term infants who received hepatitis B vaccinations at birth, 1 month, and 6 months of age according to the national immunization schedule. Venous blood samples were collected at month 6, before, and month 7 after the 3rd vaccine dose. Serum MBL, MASP-1, MASP-2, and antiHB levels were measured using commercial ELISA and chemiluminescence assays. Data were analyzed using non-parametric statistical tests and Spearman’s correlation analysis. Results: AntiHB levels increased significantly following vaccination (median Pre-3rdVac: 125.8 mIU/mL; Post-3rdVac: 609.7 mIU/mL; p < 0.001). MASP-1 concentrations also showed a significant Post-3rdVac increase (median Pre-3rdVac: 809.52 ng/mL; Post-3rdVac: 1133.93 ng/mL; p = 0.019). Birth weight was positively correlated with both MASP-1 levels (r_s = 0.492, p = 0.004) and changes in MASP-1 concentrations (r_s = 0.524, p = 0.002) after the third dose. In addition, MASP-1 levels were positively associated with antiHB levels (r_s = 0.385, p = 0.030) and Post-3rdVac antiHB titers (r_s = 0.493, p = 0.004). In contrast, serum MBL and MASP-2 concentrations were not significantly associated with antiHB levels before or after vaccination. Conclusions: MASP-1, but not MBL or MASP-2, is associated with the magnitude of the antibody response to hepatitis B vaccination in infants. These findings suggest that specific components of the lectin pathway may influence vaccine-induced immunity, independent of MBL. Further large-scale studies incorporating genetic and functional analyses are warranted to clarify the mechanisms by which lectin pathway proteins shape hepatitis B vaccine response. Full article

(This article belongs to the Special Issue Pediatric Vaccinations)

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25 pages, 3895 KB

Open AccessArticle

Evaluation of a Respiratory Syncytial Virus Subunit Vaccine Candidate in IgA-Deficient Mice: Insights into the Role of IgA in Vaccine-Induced Immunity and Protection

by Liliana Gonzalez Gonzalez, Mina Zhiani, Jourdan Witt and Sylvia van Drunen Littel-van den Hurk

Vaccines 2026, 14(1), 97; https://doi.org/10.3390/vaccines14010097 - 20 Jan 2026

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Abstract

Background/Objectives: Respiratory Syncytial Virus (RSV) causes severe disease in infants, the elderly, and immunocompromised individuals, with reinfections linked to poor induction of durable mucosal immunoglobulin A (IgA). We investigated the role of IgA in immunity and protection induced by a RSV subunit vaccine [...] Read more.

Background/Objectives: Respiratory Syncytial Virus (RSV) causes severe disease in infants, the elderly, and immunocompromised individuals, with reinfections linked to poor induction of durable mucosal immunoglobulin A (IgA). We investigated the role of IgA in immunity and protection induced by a RSV subunit vaccine candidate, tFrsc/TriAdj, which consists of a truncated RSV fusion protein (tFrsc) with a tri-component adjuvant (TriAdj). Methods: Wild-type (IgA⁺/⁺) and IgA-deficient (IgA⁻/⁻) BALB/c mice were immunized intranasally and subsequently challenged with RSV. Results: Vaccination with tFrsc/TriAdj induced robust systemic and mucosal IgG, and high lung and serum neutralizing antibodies, in both IgA⁺/⁺ and IgA⁻/⁻ mice. As expected, IgA⁻/⁻ mice lacked IgA and exhibited modest reductions in nasal IgG compared to IgA^+/+ mice following challenge, correlating to failure to clear RSV from the upper respiratory tract. In contrast, viral replication in the lungs was fully suppressed in both genotypes, indicating that IgG alone was sufficient for lower respiratory tract protection. Isotype analysis revealed diminished Th1-associated IgG2a and elevated IgG1 across mucosal and systemic compartments in IgA⁻/⁻ mice, suggesting a Th2 bias. Flow cytometric analysis confirmed reduced recruitment of IFN-γ⁺ CD4⁺ T cells in the lungs of immunized IgA⁻/⁻ mice. Interestingly, IL-17 production and numbers of IL-17⁺ CD4⁺ T cells in the lungs were increased, suggesting an enhanced Th17 response. Furthermore, IgA-deficient mice displayed reduced splenic IgG⁺ B cell populations, which is also a novel observation. Conclusions: Collectively, these findings demonstrate that although tFrsc/TriAdj confers lower airway protection in the absence of IgA, vaccine-induced IgA is critical for upper airway protection, Th1/balanced immune responses, and optimal B cell responses. Full article

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

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16 pages, 460 KB

Open AccessArticle

Trusted Sources of COVID-19 Vaccine Information by County Characteristics in North Carolina

by Bryson T. Staley, Michael E. DeWitt, Jennifer J. Wenner, John W. Sanders, Thomas F. Wierzba and Katherine Poehling

Vaccines 2026, 14(1), 96; https://doi.org/10.3390/vaccines14010096 - 20 Jan 2026

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Abstract

Background/Objectives: The COVID-19 pandemic disproportionately impacted rural areas across the United States, including rural North Carolina (NC). Consistent with national patterns, COVID-19 vaccination coverage as of December 2022 was higher for non-rural (72%) than rural (58%) NC counties. The role of trusted sources [...] Read more.

Background/Objectives: The COVID-19 pandemic disproportionately impacted rural areas across the United States, including rural North Carolina (NC). Consistent with national patterns, COVID-19 vaccination coverage as of December 2022 was higher for non-rural (72%) than rural (58%) NC counties. The role of trusted sources of vaccine information used by rural and non-rural residents is unknown. Methods: Using data from two surveys distributed by the COVID-19 Community Research Partnership from 8 June 2021 through 21 December 2021, we compared self-reported sources of trusted COVID-19 vaccine information by non-rural and rural counties and by county-level predominant political vote in the 2020 Presidential election. Results: While NC respondents were highly vaccinated (94%), fewer residents from rural counties self-reported COVID-19 vaccination than those from non-rural counties (91% versus 95%). The most common reported source of trusted vaccine information was federal health agencies. The proportion citing a federal health agency was higher for respondents from non-rural (80%) than rural (72%) counties and was higher for vaccinated (75%) than unvaccinated (42%) rural respondents. The next two most trusted sources of vaccine information were state/local health officials (48%) and health care providers (42%). Among trusted resources reported by 10–15% of respondents, those from rural counties were less likely to use hospital websites, employers, or news sources than those from non-rural counties. More respondents from counties with >60% vote for the 2020 Democratic Presidential candidate cited federal health agencies, state and local officials, and new sources than respondents from counties with >60% vote for the 2020 Republican Presidential candidate. Conclusions: By identifying the trusted sources of vaccine information for residents in non-rural and rural NC counties, future vaccine implementation efforts can tailor communication efforts to increase vaccine uptake and potentially reduce the rates of hospitalizations and death from vaccine-preventable diseases such as COVID-19 or other future pandemics. Full article

(This article belongs to the Special Issue Vaccine Hesitancy in the Era of COVID-19)

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1 pages, 115 KB

Open AccessCorrection

Correction: Wang et al. Immune Persistence Following a Single Dose of Varicella Vaccine: 5-Year and 8-Year Follow-Up of a Phase 3, Randomized, Double-Blind, Placebo-Controlled Trial. Vaccines 2025, 13, 1024

by Yanxia Wang, Xiangling Lei, Lili Huang, Yuehong Ma, Hongxue Yuan, Dongyang Zhao and Fanhong Meng

Vaccines 2026, 14(1), 95; https://doi.org/10.3390/vaccines14010095 - 20 Jan 2026

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Abstract

There was an error in the original publication [...] Full article

12 pages, 745 KB

Open AccessArticle

Epidemiological Characteristics of Mumps Under Different Immunization Strategies in Henan Province

by Zhanpei Xiao, Mingxia Lu, Yating Ma, Yan Wang, Mingyu Zhang, Binghui Du, Yiran Bai, Yuzhu Ma and Yanyang Zhang

Vaccines 2026, 14(1), 100; https://doi.org/10.3390/vaccines14010100 - 20 Jan 2026

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Abstract

Background: On 1 January 2019, a 2-dose mumps-containing vaccine (MuCV) immunization strategy was adopted in Henan Province before the national Expanded Program on Immunization (EPI). This study examines the epidemiological characteristics of mumps cases during the implementation of various immunization strategies in Henan [...] Read more.

Background: On 1 January 2019, a 2-dose mumps-containing vaccine (MuCV) immunization strategy was adopted in Henan Province before the national Expanded Program on Immunization (EPI). This study examines the epidemiological characteristics of mumps cases during the implementation of various immunization strategies in Henan Province. Methods: We employed descriptive statistics and initially retrieved data on reported cases from 2004 to 2024. Mumps case data were sourced from the China Information System for Disease Control and Prevention (CISDCP). Results: Between 2004 and 2024, a total of 301,342 cases of mumps disease were reported in Henan Province, and the average annual reported incidence was 15.11 cases per 100,000 people. The average yearly incidence decreased by 60.29% following the implementation of the 2-dose vaccination strategy compared with the one-dose strategy. The study identifies two annual incidence peaks from 2004 to 2024: a prominent peak from April to July and a smaller peak from December to January. From 2019 to 2024, in addition to a slight dip in February, the seasonality was less pronounced, with cases distributed sporadically throughout the year. The proportion of the population over 20 years old increased annually, from 8.17% in 2004–2008 to 15.55% in 2019–2024. There was an overall negative correlation between the estimated MuCV vaccination rate and the reported incidence of mumps (r = −0.685, p < 0.05). Conclusions: The introduction of 2-dose MuCV in the EPI significantly reduced the incidence rate and total number of cases. While continuing the 2-dose MuCV immunization strategy in the future, it is crucial to remain vigilant in preventing and controlling mumps among individuals over 20 years old. Full article

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17 pages, 5297 KB

Open AccessArticle

Liver Safety Assessment of an Indonesian Hexavalent Vaccine Candidate Through Histopathology and ALT/AST Evaluation in Rats and Rabbits

by Elisa D. Pratiwi, Tiza W. Mawaddah, Arif R. Sadjuri, Dimas T. Nugroho, Arip Hidayat, Astria N. Nidom, Zakiyyan I. Ayyuba, Eka S. Wahyuningsih, Kuncoro P. Santoso, Hani Plumeriastuti, Soeharsono, Setyarina Indrasari, Reviany V. Nidom, Acep R. Wijayadikusumah and Chairul A. Nidom

Vaccines 2026, 14(1), 94; https://doi.org/10.3390/vaccines14010094 - 19 Jan 2026

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Abstract

Background: Administering several separate childhood vaccines can reduce adherence to immunization schedules due to missed appointments and the burden of repeated injections. A hexavalent formulation targeting diphtheria, tetanus, pertussis, hepatitis B, Haemophilus influenzae type B, and poliovirus offers a practical approach to improve [...] Read more.

Background: Administering several separate childhood vaccines can reduce adherence to immunization schedules due to missed appointments and the burden of repeated injections. A hexavalent formulation targeting diphtheria, tetanus, pertussis, hepatitis B, Haemophilus influenzae type B, and poliovirus offers a practical approach to improve compliance and streamline immunization. Methods: Toxicity testing was performed in Wistar rats and New Zealand White rabbits (60 rats and 30 rabbits). Animals were distributed into three groups: hexavalent vaccine + low-dose sIPV, hexavalent vaccine + high-dose sIPV, and control. Each animal received a 0.5 mL intramuscular injection at weeks 0, 4, 8, and 12. Clinical observations were conducted throughout the study. Serum samples were collected one day before each injection and at the endpoint, while liver tissue was collected at the endpoint. ALT and AST concentrations were analyzed using an automated analyzer, and hepatic morphology was evaluated microscopically. Results: No abnormal clinical signs related to vaccination were observed. ALT concentrations showed no significant differences (p > 0.05). AST differences (p < 0.05) were detected between the high-dose group and the control on day 27 in female rabbits and on day 83 in female rats; however, all values remained within normal physiological limits. Histopathological examination revealed no irreversible hepatic lesions, including hydropic degeneration, portal inflammation, focal necrosis, or connective tissue proliferation, and no significant differences were noted (p > 0.05). Conclusions: Repeated administration of the hexavalent vaccine candidate at low and high doses produced no toxicological effects in animal models, supporting its safety for further clinical development. Full article

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

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24 pages, 7070 KB

Open AccessArticle

A Pool of Ferritin Nanoparticles Delivering Six Proteins of African Swine Fever Virus Induces Robust Humoral and Cellular Immune Responses in Pigs

by Zhanhao Lu, Dailang Zhong, Xin Song, Jing Lan, Yanjin Wang, Rui Luo, Shengmei Chen, Ruojia Huang, Hua-Ji Qiu, Yongfeng Li, Tao Wang and Yuan Sun

Vaccines 2026, 14(1), 93; https://doi.org/10.3390/vaccines14010093 - 19 Jan 2026

Viewed by 302

Abstract

Background/Objectives: Inadequate characterization of protective antigens poses a significant challenge to the development of vaccines for African swine fever (ASF), particularly for antigen-dependent formulations such as subunit, mRNA, and recombinant viral vector vaccines. To address this, we aimed to screen African swine [...] Read more.

Background/Objectives: Inadequate characterization of protective antigens poses a significant challenge to the development of vaccines for African swine fever (ASF), particularly for antigen-dependent formulations such as subunit, mRNA, and recombinant viral vector vaccines. To address this, we aimed to screen African swine fever virus (ASFV) antigens and enhance their immunogenicity using a nanoparticle delivery platform. Methods: Here, six ASFV antigens (p30, p54, pE120R, pH124R, pE184L, and CD2v) were purified and used to immunize pigs individually. The effects of antibodies induced by these six antigens on ASFV replication or hemadsorption was evaluated in primary porcine alveolar macrophages (PAMs). These six antigens were, respectively, conjugated to ferritin via SpyTag/SpyCatcher to prepare six ferritin nanoparticles. A cocktail of the six mixed antigens or a cocktail of the six mixed nanoparticles was used to immunize pigs separately, and the differences in induced humoral and cellular immune responses were compared. Results: Antibodies generated against p30, p54, pE120R, pH124R, and pE184L in immunized pigs significantly inhibited ASFV replication in PAMs, while anti-CD2v antibodies specifically obstructed the hemadsorption of ASFV. Notably, immunization with a cocktail of these antigen-conjugated nanoparticles elicited a stronger virus-inhibitory antibody response compared to immunization with a cocktail of antigen monomers. Furthermore, nanoparticle immunization induced robust cellular immunity, evidenced by elevated serum IFN-γ, increased numbers of ASFV-specific IFN-γ-secreting cells, and an expanded CD8⁺ T cell population. Conclusions: Our study identifies a set of promising ASFV antigen candidates and demonstrates that ferritin nanoparticle delivery synergistically enhances both humoral and cellular immune responses against ASFV, providing a rational strategy for multi-antigen ASF vaccine design. 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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18 pages, 304 KB

Open AccessArticle

HPV Vaccination Completion Among Men Who Have Sex with Men Using HIV Pre-Exposure Prophylaxis in Brazil: A Cross-Sectional Study

by Alvaro Francisco Lopes de Sousa, Lariane Angel Cepas, Isadora Silva de Carvalho, Caíque Jordan Nunes Ribeiro, Guilherme Reis de Santana Santos, Jean Carlos Soares da Silva, Talia Gomes Luz, Ruan Nilton Rodrigues Melo, Lucas Brandão dos Santos, Julia Bellini Sorrente, Gabriela Amanda Falsarella, Antonio Luis Ferreira Calaço and Ana Paula Morais Fernandes

Vaccines 2026, 14(1), 92; https://doi.org/10.3390/vaccines14010092 - 18 Jan 2026

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Abstract

Background: Men who have sex with men (MSM) using HIV pre-exposure prophylaxis (PrEP) experience a high burden of human papillomavirus (HPV) infection and related diseases, yet data on HPV vaccination among this group in Brazil remain limited. Aims: The aims of [...] Read more.

Background: Men who have sex with men (MSM) using HIV pre-exposure prophylaxis (PrEP) experience a high burden of human papillomavirus (HPV) infection and related diseases, yet data on HPV vaccination among this group in Brazil remain limited. Aims: The aims of this study were to estimate the prevalence of complete HPV vaccination and to identify factors associated with vaccination completion among MSM using PrEP in Brazil. Methods: We conducted a cross-sectional online survey between May and September 2025 among MSM aged ≥18 years, residing in Brazil and currently using oral PrEP. Participants were recruited through virtual snowball sampling and targeted advertisements on social media and a gay geosocial networking application. Data were collected using a structured, self-administered questionnaire hosted on REDCap^®. Complete HPV vaccination was defined as self-reported receipt of all doses recommended according to the participant’s age and clinical condition. Sociodemographic characteristics, relationship patterns, sexual behaviors, lubricant use during sexual activity, and history of sexually transmitted infections (STIs) were assessed. Adjusted prevalence ratios (aPRs) and 95% confidence intervals (95% CIs) were estimated using Poisson regression with robust (sandwich) variance. Results: A total of 872 MSM using PrEP were included, of whom 59.4% reported complete HPV vaccination. In adjusted analyses, complete vaccination was more frequent among participants reporting both steady and casual partners (aPR = 1.90; 95% CI: 1.36–2.65) or only casual partners (aPR = 1.72; 95% CI: 1.24–2.39), those reporting lubricant use during sexual activity (aPR = 1.41; 95% CI: 1.23–1.61), and those with a diagnosis of chlamydia and/or gonorrhea in the previous 12 months (aPR = 1.22; 95% CI: 1.08–1.36). Conclusions: Although HPV vaccination coverage among MSM using PrEP in Brazil is higher than that reported for MSM in general, it remains incomplete in a population with regular contact with specialized health services. Integrating systematic assessment and delivery of HPV vaccination into PrEP care may help increase vaccination completion and reduce missed opportunities for prevention. Full article

(This article belongs to the Special Issue Strategies to Enhance Vaccine Uptake and Immunization Among Underserved Populations/Vulnerable Groups)

16 pages, 3126 KB

Open AccessArticle

Cost-Effectiveness Analysis of a Bivalent Vaccine for Hand, Foot, and Mouth Disease: A Simulation-Based Study in Beijing, China

by Mengyao Li, Ying Shen, Yonghong Liu, Hui Yao, Zhuowei Luo, Da Huo, Xiang Xu, Wenhui Zhu, Shuaibing Dong, Lei Jia, Renqing Li, Bingyi Yang and Xiaoli Wang

Vaccines 2026, 14(1), 91; https://doi.org/10.3390/vaccines14010091 - 17 Jan 2026

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Abstract

Background: Hand, foot, and mouth disease (HFMD) remains a major public-health concern in China. While the monovalent EV-A71 vaccine has effectively reduced EV-A71–associated cases, it offers no protection against CV-A16. The introduction of a bivalent EV-A71/CV-A16 vaccine may offer broader protection, but its [...] Read more.

Background: Hand, foot, and mouth disease (HFMD) remains a major public-health concern in China. While the monovalent EV-A71 vaccine has effectively reduced EV-A71–associated cases, it offers no protection against CV-A16. The introduction of a bivalent EV-A71/CV-A16 vaccine may offer broader protection, but its economic viability under different immunization strategies remains uncertain. Methods: We developed a dynamic transmission model integrated with cost-effectiveness analysis to assess the epidemiological and economic impact of a hypothetical bivalent EV-A71/CV-A16 vaccine in China. Based on the immunization program policy, seven vaccination strategies, vaccine effectiveness (VE) levels ranging from 50–95% against EV-A71/CV-A16, and coverage levels from 0–95% were evaluated. The threshold vaccine price (TVP) was derived based on incremental cost-effectiveness ratio (ICER) calculations. Cost-effectiveness was assessed using willingness-to-pay (WTP) thresholds defined as 1–3 times the gross domestic product (GDP) per capita. Results: The mean cost of two doses of the monovalent EV-A71 vaccine was USD133.0 (95% CI: 126.9–139.1). Strategy 2, which targeted individuals unvaccinated with the monovalent EV-A71 vaccine, demonstrated the most favorable cost-effectiveness. At 45% coverage and 85% vaccine effectiveness, the estimated threshold price per dose was USD 107.7 (95% CI: 103.4–112.0), with threshold vaccine prices increasing as coverage declined. When vaccination coverage exceeded 80%, the threshold vaccine price decreased substantially, falling below USD 45.9 (95% CI: 43.5–48.3) per dose. Conclusions: Large-scale inclusion in the national immunization program may not be economically justified at current cost levels. Targeted voluntary vaccination of unvaccinated, susceptible populations represents a more cost-effective and practical strategy during the early stage of vaccine introduction. Full article

(This article belongs to the Special Issue Vaccine Efficacy and Disease Burden Evaluation)

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13 pages, 1048 KB

Open AccessArticle

Heterogeneity in the Association Between Pneumococcal Vaccination and the Risk of Severe Community-Acquired Pneumonia in Elderly Inpatients: A Causal Forest Analysis

by Yunhua Lan, Ziyi Xin, Zhuochen Lin, Jialing Li, Xin Xie, Ying Xiong and Dingmei Zhang

Vaccines 2026, 14(1), 90; https://doi.org/10.3390/vaccines14010090 - 16 Jan 2026

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Abstract

Background: Community-acquired pneumonia (CAP) is a leading cause of morbidity and mortality in the elderly. While pneumococcal vaccination is a core preventive measure, it remains unclear whether its association with severe CAP is uniform across all elderly subgroups. Our study aimed to evaluate [...] Read more.

Background: Community-acquired pneumonia (CAP) is a leading cause of morbidity and mortality in the elderly. While pneumococcal vaccination is a core preventive measure, it remains unclear whether its association with severe CAP is uniform across all elderly subgroups. Our study aimed to evaluate the overall association of pneumococcal vaccination with the risk of severe CAP in hospitalized patients aged ≥ 65 years and to explore potential heterogeneity in this association using a causal forest model. Methods: We conducted a retrospective cohort study of patients discharged between January 2023 and June 2025, aged ≥ 65 years, with a primary diagnosis of CAP. We used multivariable logistic regression to estimate the average association and a causal forest model to explore heterogeneous patterns in the conditional average treatment effect (CATE). Results: Among 1906 included patients (severe CAP: 924; non-severe CAP: 982), PPSV23 vaccination was independently associated with reduced odds of all-cause severe CAP (adjusted OR = 0.610, 95% CI: 0.401–0.930). The causal forest model yielded an average treatment effect (ATE) estimate of −0.112 (95% CI: −0.200 to −0.023), corresponding to an 11.2 percentage-point reduction in absolute risk. Exploratory analysis suggested potential heterogeneity: the association appeared most pronounced in patients aged 65–74 years (CATE = −0.122) and showed an attenuating trend in older groups. Age was the primary variable associated with heterogeneity, followed by hypertension, SARS-CoV-2 infection, and sex. Conclusions: In this observational cohort study, PPSV23 vaccination was associated with a reduced risk of severe CAP in elderly inpatients under strong assumptions of no unmeasured confounding. Exploratory analyses suggested potential heterogeneity in this association, which appeared to attenuate with advancing age and may be influenced by comorbidities. These hypothesis-generating findings indicate that further investigation is needed to determine whether prevention strategies should be tailored for the very old and those with specific chronic conditions. Full article

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

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12 pages, 1426 KB

Open AccessArticle

Protection Against Salmonella by Vaccination with Toxin–Antitoxin Self-Destructive Bacteria

by Nady Gruzdev, Jacob Pitcovski, Chen Katz, Nili Ruimi, Dalia Eliahu, Caroline Noach, Ella Rosenzweig, Avner Finger and Ehud Shahar

Vaccines 2026, 14(1), 89; https://doi.org/10.3390/vaccines14010089 - 15 Jan 2026

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Abstract

Background: Salmonella is a major zoonotic foodborne pathogen. Conventional poultry vaccines may present limitations in terms of efficacy, safety, and practicality. Objectives: This study focuses on enhancing the immunogenicity and improving the safety of a novel oral vaccination employing inducible toxin–antitoxin [...] Read more.

Background: Salmonella is a major zoonotic foodborne pathogen. Conventional poultry vaccines may present limitations in terms of efficacy, safety, and practicality. Objectives: This study focuses on enhancing the immunogenicity and improving the safety of a novel oral vaccination employing inducible toxin–antitoxin (TA) systems, which lead to self-destruction of virulent Salmonella Enteritidis. Methods: A Hok/Sok (HS) TA system was designed to induce cell death upon absence of arabinose. Point mutations were introduced to the Hok toxin promoter to moderate toxin production. A combination of HS and CeaB/CeiB (CC) TA systems was designed to induce cell death both in low di-cation levels or anaerobic conditions. Survival of Salmonella-carrying TA systems was tested in culture and in the Raw264.7 macrophage cell line. One-day old chicks were inoculated with Salmonella carrying the TA system to evaluate bacterial persistence and induction of a protective immune response. Results: Attenuation of the Hok toxin promoter prolonged bacterial survival in vitro. Salmonella carrying the combined TA systems was eliminated completely both in vitro and in inoculated chickens, eliciting high levels of antibodies and conferring protection against challenge with wild-type Salmonella. Conclusions: These findings highlight the potential of the adaptable TA-based vaccination platform to generate safe and efficacious Salmonella vaccines for poultry, contributing to reduced transmission in the food chain. Full article

(This article belongs to the Special Issue New Approaches to Vaccine Development and Delivery)

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22 pages, 3507 KB

Open AccessArticle

Extending ImmunoSpot^® Assays’ Sensitivity for Detecting Rare Antigen-Specific B Cells to One in a Million—And Possibly Lower

by Greg A. Kirchenbaum, Noémi Becza, Lingling Yao, Alexey Y. Karulin and Paul V. Lehmann

Vaccines 2026, 14(1), 88; https://doi.org/10.3390/vaccines14010088 - 15 Jan 2026

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Abstract

Background/Objectives: Despite clonal expansion during a primary immune response, or after subsequent antigen encounters, the frequency of memory B cells (B_mem) specific for an antigen remains low, making their detection difficult. However, unlike serum antibodies, which have a short half-life [...] Read more.

Background/Objectives: Despite clonal expansion during a primary immune response, or after subsequent antigen encounters, the frequency of memory B cells (B_mem) specific for an antigen remains low, making their detection difficult. However, unlike serum antibodies, which have a short half-life in vivo and thus require continuous replenishment to maintain stable titers, circulating B_mem are long-lived; they preserve immunological preparedness through their ability to rapidly engage in recall responses and differentiate into antibody-secreting cells (ASCs) upon antigen encounter. To this end, development of assays suited for the reliable detection of rare antigen-specific B_mem is critical and can provide insights into an individual’s antigen exposure history and immune status beyond that offered by traditional serum antibody measurements alone. Methods: ImmunoSpot^® has emerged as a suitable technique for the detection of individual antigen-specific B cells through visualizing their antibody-derived secretory footprints. Here, we report the theoretical and practical foundations for detecting rare antigen-specific B_mem in human peripheral blood mononuclear cells (PBMC). Leveraging the unique availability of verifiably naïve vs. antigen-experienced human samples, we used SARS-CoV-2 Spike (S-) and Nucleocapsid (NCAP) antigens to interrogate the presence of B_mem with these respective specificities. Results: While 100% diagnostic accuracy was achieved for both antigens, detection of NCAP-specific B_mem required reducing the lower detection limit of the standard assay. Specifically, this was achieved by testing a total of 2 million PBMC across multiple replicate assay wells and assessing the cumulative number of secretory footprints detected. Conclusion: The protocols described here should facilitate the reliable detection of ASCs present at varying precursor frequencies and serve as guidance for routine immune monitoring of rare B_mem with specificity for any antigen. Full article

(This article belongs to the Special Issue Human Immune Responses to Infection and Vaccination)

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19 pages, 2851 KB

Open AccessArticle

Adenovector 26 Encoded RSV Prefusion F Protein (Ad26.RSV.preF) Does Not Predispose to Enhanced Respiratory Disease in Preclinical Rodent Models

by Renske Bolder, Susan B. S. King, Roland C. Zahn and Leslie van der Fits

Vaccines 2026, 14(1), 87; https://doi.org/10.3390/vaccines14010087 - 15 Jan 2026

Viewed by 335

Abstract

Background/objectives: RSV is a major cause of mortality in infants, and despite recent progress to prevent RSV in the very young, an RSV vaccine for this population is still highly warranted. Clinical studies in infants in the 1960s using formalin-inactivated RSV (FI-RSV) led [...] Read more.

Background/objectives: RSV is a major cause of mortality in infants, and despite recent progress to prevent RSV in the very young, an RSV vaccine for this population is still highly warranted. Clinical studies in infants in the 1960s using formalin-inactivated RSV (FI-RSV) led to life-threatening enhanced respiratory disease (ERD). Therefore, a thorough safety assessment of RSV vaccine candidates intended for RSV seronegative infants is crucial. Methods: Prior to clinical pediatric development of Ad26.RSV.preF, an adenovirus type 26 vector-encoding RSV F protein stabilized in its prefusion conformation, predisposition to ERD was extensively assessed in cotton rat and mouse models. Results: Cotton rats intramuscularly immunized with a wide dose range of Ad26.RSV.preF, including low and sub-protective vaccine doses, and challenged with vaccine homologous RSV A2 or heterologous RSV B Wash 18537, did not show signs of predisposition to ERD. Histopathology scores for alveolitis, peribronchiolitis, interstitial pneumonia, and perivasculitis after challenge were significantly lower for Ad26.RSV.preF-immunized cotton rats compared to FI-RSV-immunized cotton rats and comparable to or lower than scores in cotton rats intranasally pre-exposed to RSV prior to challenge to mimic natural repeated infection. These results were observed in animals with or without viral replication in the lung after RSV challenge, in the presence or absence of vaccine-induced antibodies. Similar results were observed in mice, where more extensive assessment of mono- and polymorphonuclear cell alveolitis, mucus cell hyperplasia, and mucus accumulation was performed. Conclusions: Based on these extensive analyses, we conclude that there are no indications of ERD predisposition after Ad26.RSV.preF vaccination in rodent models, irrespective of the vaccine dose, challenge virus strain, or presence of viral replication in the lung. These results are crucial for the pediatric development of this 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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4 pages, 140 KB

Open AccessEditorial

Promoting Vaccination in the Post-COVID-19 Era

by Zoi Tsimtsiou

Vaccines 2026, 14(1), 86; https://doi.org/10.3390/vaccines14010086 - 15 Jan 2026

Viewed by 266

Abstract

During the COVID-19 pandemic, substantial changes occurred that may have either facilitated or hindered efforts to promote vaccination [...] Full article

(This article belongs to the Special Issue Promoting Vaccination in the Post-COVID-19 Era)

8 pages, 211 KB

Open AccessArticle

Family Decision to Immunize Against Respiratory Syncytial Virus and Associations with Seasonal Influenza and COVID-19 Vaccination

by Leah D. Kaye, Benjamin N. Fogel, Ruth E. Gardner, Brody J. Lipsett, Katherine E. Shedlock, Eric W. Schaefer, Ian M. Paul and Steven D. Hicks

Vaccines 2026, 14(1), 85; https://doi.org/10.3390/vaccines14010085 - 14 Jan 2026

Viewed by 349

Abstract

Background: Nirsevimab, a monoclonal antibody for respiratory syncytial virus (RSV), reduces medically attended RSV infections. It was introduced in the 2023–24 RSV season. This study examined the association between caregiver vaccination (seasonal influenza vaccine (SIV), COVID-19, and boosters) and intent to immunize infants [...] Read more.

Background: Nirsevimab, a monoclonal antibody for respiratory syncytial virus (RSV), reduces medically attended RSV infections. It was introduced in the 2023–24 RSV season. This study examined the association between caregiver vaccination (seasonal influenza vaccine (SIV), COVID-19, and boosters) and intent to immunize infants against RSV. Methods: Data from 118 caregivers with infants ≤ 8 months were analyzed. Chi-squared tests and logistic regression assessed the relationship between caregiver vaccination and intent to immunize against RSV. Results: In total, 74.6% of caregivers intended to immunize their infants against RSV. Intent was positively associated with caregiver receipt of a seasonal influenza vaccine (p < 0.001), COVID-19 vaccine (p < 0.001), and COVID-19 booster (p < 0.001). Intent was also associated with older child seasonal vaccination. Caregiver receipt of both COVID-19 vaccinations and boosters had a strong relationship with RSV immunization intent (OR 7.91 (1.90–33.0, p = 0.004)). Conclusions: Caregiver vaccination behaviors are linked to RSV immunization intent, helping physicians identify hesitant families and prepare for immunization conversations. Full article

(This article belongs to the Special Issue Recent Progress of Vaccines for Respiratory Syncytial Virus (RSV))

18 pages, 1680 KB

Open AccessArticle

Exploratory Evaluation of Peptide-Based Immunization Targeting Fusion Glycoprotein-Derived Epitopes of Nipah Virus in Murine Model

by Seo Young Moon, Rochelle A. Flores, Eun Bee Choi, Seungyeon Kim, Hyunjin Je, Eun Young Jang, Heeji Lim, Yoo-Kyoung Lee, In-Ohk Ouh and Woo H. Kim

Vaccines 2026, 14(1), 84; https://doi.org/10.3390/vaccines14010084 - 13 Jan 2026

Viewed by 550

Abstract

Background: Nipah virus (NiV), a zoonotic paramyxovirus with high case fatality and pandemic potential, remains without a licensed vaccine for humans to date. Although there has been progress in vaccine development, it remains limited, and peptide vaccines have rarely been validated in vivo. [...] Read more.

Background: Nipah virus (NiV), a zoonotic paramyxovirus with high case fatality and pandemic potential, remains without a licensed vaccine for humans to date. Although there has been progress in vaccine development, it remains limited, and peptide vaccines have rarely been validated in vivo. Methods: Here, we report the rational antigen selection, synthesis, and preliminary immunogenicity evaluation of NiV fusion glycoprotein (NiV-F)-derived linear peptides as vaccine candidates. Candidate epitopes were identified by in silico, and a total of 18 B- and T-cell epitope-derived peptides were shortlisted for synthesis and antigenicity validation by ELISA. Results: Antigenicity evaluation showed that 9 of the synthesized peptides have A_450nm of over 1 (8 from the F11 group, A_450nm: 1.13–3.6; 1 from the F18 group, A_450nm: 1.51), with the peptide constructs F11-3 (A_450nm: 3.5) and F11-4 (A_450nm: 3.6) showing the highest antigenicity. Interestingly, peptides from F11 with amidation increased antibody binding (F11-4-NH2, A_450nm: 3.05; F11-4-9mer-1-NH2, A_450nm: 0.87). The lead peptide candidates, F11-3 and F11-4, were subsequently used for the immunization experiment, and mouse sera were assessed against their homologous peptide antigens or recombinant NiV-F protein. ELISA result showed detectable antibody reactivity against their homologous antigen for the intramuscular (IM) F11-3 vaccinated group (A_450nm: 0.30 ± 0.35), whereas increased binding was observed for both IM-administered F11-3 (A_450nm: 1.62 ± 0.97) and F11-4 (A_450nm: 2.0 ± 0.77) against NiV-F protein, albeit without statistical significance compared to the negative control (NC, p > 0.05), and were markedly lower compared to mice immunized with NiV-F recombinant protein (PC, p < 0.01), underscoring the need for further optimization procedures. Conclusions: Collectively, these results support an exploratory antigen discovery and prioritization framework for NiV-F-derived peptide candidates and provide a foundation for future studies aimed at optimizing immunogenicity and evaluating protective relevance in appropriate preclinical models. Full article

(This article belongs to the Special Issue Novel Vaccines and Vaccine Technologies for Emerging Infections)

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6 pages, 156 KB

Open AccessEditorial

Myriad Pathways to Universality: How Widely Sourced Data, Use of Frameworks and Innovative Analytic Methods Help Tackle Immunization Inequality

by Devaki Nambiar, Ahmad Reza Hosseinpoor, Nicole Bergen, M. Carolina Danovaro-Holliday, Ibrahim Dadari and Hope L. Johnson

Vaccines 2026, 14(1), 83; https://doi.org/10.3390/vaccines14010083 - 13 Jan 2026

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Abstract

Great strides have been made in the area of immunization over the past several decades [...] Full article

(This article belongs to the Special Issue Inequality in Immunization 2025)

28 pages, 2582 KB

Open AccessArticle

Efficacy of Plasmid DNA Delivery into Mice by Intradermal Injections Alone and Facilitated by Sonoporation or Electroporation

by Daria Avdoshina, Vladimir Valuev-Elliston, Maria Belikova, Alla Zhitkevich, Anastasia Latanova, Galina Frolova, Oleg Latyshev, Ilya Gordeychuk and Ekaterina Bayurova

Vaccines 2026, 14(1), 82; https://doi.org/10.3390/vaccines14010082 - 12 Jan 2026

Viewed by 324

Abstract

Background/Objectives: A key disadvantage of DNA vaccines is ineffective uptake of plasmid DNA, resulting in low immunogenicity. A way to overcome it is forced DNA delivery, which requires specialized equipment and/or reagents. Effective delivery of plasmids without specialized devices or using commonly [...] Read more.

Background/Objectives: A key disadvantage of DNA vaccines is ineffective uptake of plasmid DNA, resulting in low immunogenicity. A way to overcome it is forced DNA delivery, which requires specialized equipment and/or reagents. Effective delivery of plasmids without specialized devices or using commonly available ones would significantly increase DNA vaccine applicability. Here, we delivered DNA by intradermal injections, facilitating them by optimized sonoporation (SP) or electroporation (EP), and we compared these methods by their capacity to support the production of foreign proteins in mice. Methods: DNA delivery was optimized using the plasmid encoding firefly luciferase (Luc) (pVaxLuc). Luc production was assessed by bioluminescence imaging (BLI) (IVIS, PerkinElmer, Shelton, CT, USA; LumoTrace Fluo, Abisense, Dolgoprudny, Russia). Female BALB/c mice were injected intradermally (id) with pVaxLuc in phosphate buffers of varying ionic strengths. Injection sites were subjected to SP (Intelect Mobile, Chattanooga, UK) or EP (CUY21EDITII, BEX Co., Tokyo, Japan) or left untreated. Optimal delivery protocols were selected based on the highest in vivo levels of photon flux according to BLI. Optimal protocols for id injections with/without EP were applied to DNA-immunized mice with HIV-1 clade A reverse transcriptase. Antibody response induced by DNA immunization was assessed by ELISA. Results: The optimal phosphate buffers for id delivery had ionic strengths from 81 to 163 mmol/L. The optimal SP regimen included an acoustic pressure of 2.4 W/cm² applied in a duty cycle of 2%. The optimal EP regimen included bipolar driving pulses of 100 V, a pulse duration of 10 ms, and an interval between the pulses of 20 ms. Optimized DNA delivery by id/SP injection was inferior to both id/EP and id alone. DNA immunization with HIV-1 RT by id injections induced anti-RT antibodies in a titer of 10⁴ and by id/EP in a titer of 10⁵. Conclusions: Electroporation of the sites of id DNA injection provided the highest levels of production of luciferase reporters and induced a strong antibody response against HIV-1 RT. Full article

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

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22 pages, 783 KB

Open AccessReview

Plant Viral Vectors for Vaccine Development

by Mehdi Shahgolzari, Afagh Yavari, Srividhya Venkataraman, Mehrin Faija and Kathleen Hefferon

Vaccines 2026, 14(1), 81; https://doi.org/10.3390/vaccines14010081 - 12 Jan 2026

Viewed by 426

Abstract

Plant viruses are useful tools for quickly and easily producing recombinant proteins in plants. Compared to systems that use genetically modified plants, viral vectors are easier to work with and can produce recombinant proteins faster and in larger amounts. Recently, there has been [...] Read more.

Plant viruses are useful tools for quickly and easily producing recombinant proteins in plants. Compared to systems that use genetically modified plants, viral vectors are easier to work with and can produce recombinant proteins faster and in larger amounts. Recently, there has been growing interest in using plant viruses as vectors to make vaccines, either as whole proteins or as small parts displayed on plant virus particles. The best examples for this purpose are tobacco mosaic virus, cowpea mosaic virus and potato virus X. Vaccines made using these viruses target various human and animal diseases and have often triggered immune responses and provided protection against infections. This review looks at the benefits of using plant virus vectors, the progress in developing different viral vector systems, and immune studies that support the idea of vaccines made from plant viruses. Full article

(This article belongs to the Special Issue Strategies of Viral Vectors for Vaccine Development)

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19 pages, 4966 KB

Open AccessArticle

Self-Multimerization of mRNA LNP-Derived Antigen Improves Antibody Responses

by Cody A. Despins, James Round, Lisa Dreolini, Tracy S. Lee, Scott D. Brown and Robert A. Holt

Vaccines 2026, 14(1), 80; https://doi.org/10.3390/vaccines14010080 - 12 Jan 2026

Viewed by 454

Abstract

Background: mRNA LNP technology is now being widely applied as a highly effective vaccine platform. Antigen multimerization is a well-established approach to enhance the antibody titers and protective efficacy of several protein subunit vaccines. However, this approach has been less explored for [...] Read more.

Background: mRNA LNP technology is now being widely applied as a highly effective vaccine platform. Antigen multimerization is a well-established approach to enhance the antibody titers and protective efficacy of several protein subunit vaccines. However, this approach has been less explored for mRNA LNP vaccines. Methods: Here, within the context of mRNA LNP vaccination, we used mStrawberry (mSb) as a model antigen to conduct a comprehensive, head-to-head comparison of the ability of the foldon (3-mer), IMX313 (7-mer), and ferritin (24-mer) multimerization domains to enhance immunogenicity in mice. Results: We compared multimerized antigen to monomeric secreted antigen and monomeric surface-displayed antigen and observed that the IMX313 domain efficiently multimerized mSb protein and significantly enhanced anti-mSb antibody titers, whereas the foldon and ferritin domains failed to multimerize or improve antibody levels. Conclusions: Our results extend the observation of improved immunogenicity from antigen multimerization to mRNA LNP vaccines and indicate that the 7-mer forming IMX313 multimerization domain may be an ideal candidate for multimer formation in the context of mRNA LNP vaccination. Future studies are needed to evaluate the multimerization of pathogen-derived antigens, in the mRNA LNP format, for the enhancement of neutralization and protective efficacy. Full article

(This article belongs to the Special Issue Feature Papers of DNA and mRNA Vaccines)

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Vaccines, Volume 14, Issue 1 (January 2026) – 109 articles

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