Vaccines

23 pages, 5245 KB

Open AccessArticle

Virus-like and Virus Replicon Particles Targeting Multiple B-Cell Antigens Do Not Protect Against African Swine Fever Virus

by Kirill Lotonin, Obdulio García-Nicolás, Normann Kilb, Stefan Krämer, Xinyue Chang, Paul Engeroff, Kemal Mehinagic, Noelle Donzé, Francisco Brito, Matthias Liniger, Ilva Lieknina, Darja Cernova, Ieva Balta, Gabriela González-García, Paloma Rueda, Gert Zimmer, Charaf Benarafa, Nicolas Ruggli, Günter Roth, Kaspars Tars, Martin Bachmann and Artur Summerfield Show full author list Hide full author list

Vaccines 2026, 14(3), 285; https://doi.org/10.3390/vaccines14030285 - 23 Mar 2026

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Abstract

Background: African swine fever virus (ASFV) causes a fatal hemorrhagic disease in domestic pigs and wild boars. While live attenuated vaccines (LAVs) provide protection, their use raises safety concerns. Therefore, the aim of the present study was to identify viral B-cell antigens [...] Read more.

Background: African swine fever virus (ASFV) causes a fatal hemorrhagic disease in domestic pigs and wild boars. While live attenuated vaccines (LAVs) provide protection, their use raises safety concerns. Therefore, the aim of the present study was to identify viral B-cell antigens associated with protection and to test their potential using highly immunogenic vaccine delivery platforms. Methods: We employed a microarray of 169 ASFV proteins expressed in a cell-free prokaryotic system to identify immunodominant antigens using sera from immune pigs. Six structural proteins were selected and formulated into AP205 virus-like particles (VLPs). Additionally, replication-defective vesicular stomatitis virus (VSV)-based vaccine candidates expressing glycosylated CD2v and EP153R proteins were generated. Three groups of specific pathogen-free pigs were immunized with either VLP- or VSV-based vaccines and challenged with the virulent ASFV Georgia 2007 strain. Control groups included pigs immunized with the attenuated ASFV Estonia 2014 strain and a naïve group. Results: Most vaccine candidates induced detectable antibody responses against target ASFV proteins. However, neither VLP- nor VSV-based vaccines provided protection, as clinical scores, hematology, cytokine responses, and viremia levels were similar to those in the negative control group. In contrast, only the ASFV Estonia 2014 strain elicited a robust T-cell response and protective immunity. Conclusions: These findings highlight the challenges in identifying protective B-cell antigens of ASFV and emphasize the pivotal role of cellular immunity in mediating protection. Full article

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

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21 pages, 1846 KB

Open AccessReview

The Prospects and Challenges of Live Attenuated Vaccines Against African Swine Fever Virus in Vietnam

by Tram Thi Ngoc Ngo, Taehwan Oh and Duy Tien Do

Vaccines 2026, 14(3), 284; https://doi.org/10.3390/vaccines14030284 - 23 Mar 2026

Viewed by 755

Abstract

African swine fever (ASF) is a contagious viral disease that causes severe economic losses in the global swine industry. Since its introduction to Vietnam in 2019, ASFV has evolved rapidly, with genotype II strains dominating initially and recombinant I/II variants emerging by 2023. [...] Read more.

African swine fever (ASF) is a contagious viral disease that causes severe economic losses in the global swine industry. Since its introduction to Vietnam in 2019, ASFV has evolved rapidly, with genotype II strains dominating initially and recombinant I/II variants emerging by 2023. Live attenuated vaccines (LAVs) have been developed and commercialized in Vietnam, including ASFV-G-ΔI177L, ASFV-G-ΔI177L/ΔLVR, and ASFV-G-ΔMGF, which confer homologous immune protection. Despite this, LAVs face challenges related to genetic stability, impossible protection against emerging recombinant strains, potential reversion to virulence, viral shedding, and safety in pregnant sows. ASFV’s ongoing evolution underscores the need for continuous genomic surveillance, evaluation of cross-protective efficacy, and implementation of biosecurity and DIVA strategies focused more on evaluating vaccine efficacy than safety. This review summarizes the current molecular epidemiology of ASFV in Vietnam after vaccines were licensed for use, the development and performance of commercial LAVs, and the practical challenges of their application in endemic settings, and provides insights for informed vaccine deployment and integrated ASF control strategies in rapidly evolving viral landscapes. Full article

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34 pages, 1468 KB

Open AccessReview

SARS-CoV-2 and Influenza Co-Circulation and Co-Vaccination: A Narrative Review

by Mohammad Kamransarkandi, Elena A. Varyushina, Andrey N. Gorshkov and Marina A. Stukova

Vaccines 2026, 14(3), 283; https://doi.org/10.3390/vaccines14030283 - 23 Mar 2026

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Abstract

Background/Objectives: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza virus are dangerous respiratory pathogens with high pandemic potential. Since 2021, these two viruses have been co-circulating, which implies additional risks of co-infection with both pathogens. Prophylactic vaccination is widely recognized as the [...] Read more.

Background/Objectives: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza virus are dangerous respiratory pathogens with high pandemic potential. Since 2021, these two viruses have been co-circulating, which implies additional risks of co-infection with both pathogens. Prophylactic vaccination is widely recognized as the most effective way to prevent COVID-19 and influenza and to reduce the severity of these diseases. This review analyzes recent data on the simultaneous circulation of influenza and SARS-CoV-2 viruses worldwide, including epidemiological data and the pathogenetic mechanisms of co-infection. Next, we focus on current approaches to simultaneous and combined vaccination against influenza and COVID-19. We outline the types of vaccines and summarize the available findings on the effectiveness and safety of co-vaccination. Methods: A comprehensive search was conducted using PubMed, Scopus, Web of Science, and ClinicalTrials to identify data relevant to SARS-CoV-2 and influenza co-circulation and dual vaccination. Results: Influenza and SARS-CoV-2 cause similar symptoms, and co-infection can significantly enhance the risks of pneumonia and acute respiratory distress syndrome progressing with a poor outcome, especially among children and the elderly. A range of influenza and COVID-19 vaccines built on different technological platforms is currently available on the market, with proven effectiveness, immunogenicity, and safety. A co-vaccination approach is more convenient for patients and is associated with better response to treatment, while also improving vaccine coverage and compliance and offering significant resource savings for healthcare systems. Conclusions: The concurrent circulation of SARS-CoV-2 and influenza viruses presents a growing public health challenge. Simultaneous and combination vaccination strategies have emerged as effective tools to streamline immunization, enhance protection, and reduce healthcare burden. Future studies should elucidate the mechanisms of the exacerbation of respiratory disease caused by co-infection, as well as the optimal strategies for co-administering influenza and COVID-19 vaccines for long-term control of seasonal and potentially pandemic respiratory viruses. Full article

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20 pages, 2287 KB

Open AccessArticle

Lambda Phage-Based Antibody-Stimulating Platform Targeting EGFRvIII

by Meredith Bush, Manoj Rajaure, Calla Gentilucci, Phuoc Le, Xintian Li and Sankar Adhya

Vaccines 2026, 14(3), 282; https://doi.org/10.3390/vaccines14030282 - 23 Mar 2026

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Abstract

Background/Objectives: Bacteriophage-based display has been utilized for a variety of purposes, such as to assemble protein libraries and conduct biopanning. We have created a modified lambda (λ) bacteriophage platform, ideal for the display and delivery of proteins. Our system utilizes counter-selection recombineering for [...] Read more.

Background/Objectives: Bacteriophage-based display has been utilized for a variety of purposes, such as to assemble protein libraries and conduct biopanning. We have created a modified lambda (λ) bacteriophage platform, ideal for the display and delivery of proteins. Our system utilizes counter-selection recombineering for versatile modification, temperature-sensitive induction for timely lysate production, and an arabinose-inducible mechanism for high-titer, stable yield. Here, we investigated the ability of this specialized λ phage display platform to stimulate highly specific antibodies in mice against the displayed cancer-variant cell-surface receptor EGFRvIII, demonstrating its potential in cancer immunotherapy and broader vaccine development. Methods: λ display immunogenicity was explored by generating fusion proteins between the λ head protein D and a 13-mer peptide from the N terminus of glioblastoma variant cell-surface receptor, EGFRvIII. The 13-mer peptide was fused to either the N or C terminus of the λD protein while λ remained a dormant lysogen in the bacterial host chromosome. Recombinant phage lysates were then generated with ~420 displayed fusion proteins per phage particle. Mice were injected with purified recombinant λ phage without an adjuvant via both intraperitoneal and intramuscular routes, and sera harvested at various timepoints were profiled for immunogenicity. Results: Analysis of serum samples by ELISA and Western blotting demonstrated the ability of the λD~EGFRvIII phage display, especially in the C-terminal fusion construction, to elicit a robust anti-EGFRvIII humoral response by either injection route. Notably, the antibody response was highly specific to EGFRvIII without exhibiting cross-reactivity to wild-type EGFR. Conclusions: The data generated in this study demonstrate the λ system’s immunotherapeutic potential as a high-titer, stable, self-adjuvanting vector for the stimulation of robust antibody titers with defined specificity. Full article

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

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19 pages, 3119 KB

Open AccessArticle

Structural Design of T-Cell Epitope-Based mRNA Vaccine Constructs Determines the Quality of T-Cell Immunity and Protective Efficacy Against SARS-CoV-2 in Mice

by Vladimir A. Gushchin, Andrei E. Siniavin, Andrei A. Pochtovyi, Alina S. Dzharullaeva, Dmitriy N. Shcherbinin, Anastasia S. Ungur, Amir I. Tukhvatulin, Inna V. Shuliakova, Denis A. Kleymenov, Elena P. Mazunina, Evgeniia N. Bykonia, Sofia R. Kozlova, Evgeny V. Usachev, Ilya D. Zorkov, Daria M. Grousova, Anna A. Iliukhina, Alexander L. Gintsburg and Denis Y. Logunov

Vaccines 2026, 14(3), 281; https://doi.org/10.3390/vaccines14030281 - 23 Mar 2026

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Abstract

Background/Objectives: Epitope-based mRNA vaccines represent a promising strategy for eliciting protective T-cell immunity against SARS-CoV-2 and as well as for non-infectious mRNA-based vaccines. However, how the structural architecture of vaccine constructs (including epitope arrangement, linker composition, signal peptide presence, and the combination of [...] Read more.

Background/Objectives: Epitope-based mRNA vaccines represent a promising strategy for eliciting protective T-cell immunity against SARS-CoV-2 and as well as for non-infectious mRNA-based vaccines. However, how the structural architecture of vaccine constructs (including epitope arrangement, linker composition, signal peptide presence, and the combination of MHC class I and II epitopes) shapes the quality of T-cell responses remains poorly understood. Methods: Ten tandem minigene mRNA constructs (Cons1–10) encoding different combinations of MHC class I and class II epitopes from SARS-CoV-2 proteins (S, N, M, ORF3a) were designed, encapsulated in lipid nanoparticles, and administered to C57BL/6 mice. Immunogenicity was assessed by cytokine profiling (IFN-γ, IL-2, IL-4, IL-10) and T-cell proliferation assays. Protective efficacy was evaluated in K18-hACE2 transgenic mice challenged with SARS-CoV-2. Results: Constructs lacking a signal peptide and enriched in MHC class I-restricted epitopes induced robust Th1 responses and strong CD8⁺ T-cell proliferation, achieving up to 66% survival following lethal challenge. In contrast, constructs associated with elevated IL-10 and IL-4 production conferred limited protection (11–33%), consistent with functional skewing towards regulatory or Th2-associated immune profiles. Conclusions: These findings establish a direct link between construct design parameters and T-cell polarization quality, and provide a rational framework for next-generation epitope-based mRNA vaccine development. Full article

(This article belongs to the Special Issue The Development of mRNA Vaccines)

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12 pages, 311 KB

Open AccessArticle

Baseline Hepatitis B Immunity and Vaccination Booster Response Among Medical Residents: A Longitudinal Study in a Spanish Tertiary Hospital

by Victoria Salguero-Cano, Silvia Martínez-Martínez, Manuel González-Alcaide, Carmen Valero-Ubierna, Virginia Martínez-Ruiz, Mario Rivera-Izquierdo and Inmaculada Guerrero-Fernández de Alba

Vaccines 2026, 14(3), 280; https://doi.org/10.3390/vaccines14030280 - 23 Mar 2026

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Abstract

Background: Despite universal infant hepatitis B virus (HBV) vaccination, declining circulating anti-HBs levels are increasingly observed in young healthcare professionals, a high-risk group for occupational exposure. Although several studies have evaluated HBV antibody persistence in healthcare workers, data specifically addressing newly incorporated medical [...] Read more.

Background: Despite universal infant hepatitis B virus (HBV) vaccination, declining circulating anti-HBs levels are increasingly observed in young healthcare professionals, a high-risk group for occupational exposure. Although several studies have evaluated HBV antibody persistence in healthcare workers, data specifically addressing newly incorporated medical residents in the Spanish context remain limited. This study evaluated baseline anti-HBs levels and serological response to a vaccination booster dose in medical residents at a Spanish tertiary hospital. Methods: A retrospective longitudinal observational study was conducted among medical residents attending the Preventive Medicine Service of Hospital Universitario San Cecilio (Granada, Spain) between 2021 and 2024. Anti-HBs antibody titers were obtained at baseline and ≥10 mIU/mL were considered the conventional protective threshold. Residents with anti-HBs < 10 mIU/mL received an Engerix-B booster followed by repeat serology. Demographic and occupational variables were analyzed. Measles serostatus was collected for comparisons. Results: A total of 275 residents were included (mean age 25.4 years, SD = 2.3 years; 64% females). Baseline serology showed anti-HBs levels < 10 mIU/mL in 53.1% of participants. Lower baseline anti-HBs levels were associated with younger age (adjusted OR = 0.75; 95% CI: 0.64–0.88) and earlier residency year (R1–R2) (adjusted OR = 0.28; 95% CI: 0.13–0.61). Among 116 residents receiving a booster, 94.8% achieved anti-HBs ≥ 10 mIU/mL after booster administration. Measles serology was negative in 54.6% of participants. Conclusions: More than half of newly incorporated medical residents had anti-HBs levels below the conventional protective threshold (10 mIU/mL), yet almost all demonstrated a strong anamnestic response, supporting the persistence of immunological memory despite reduced circulating antibody concentrations. Systematic baseline screening combined with targeted booster vaccination appears to be an effective strategy to ensure occupational protection. Further research incorporating cellular immunity markers may refine future vaccination policies and booster strategies. Full article

(This article belongs to the Special Issue Vaccination Against Viral Hepatitis for Prevention and Treatment)

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15 pages, 3015 KB

Open AccessArticle

An Oral Vaccine Derived from Attenuated Salmonella Producing Murine Cytomegalovirus M24 Protein Induces Successful Antiviral Immune Responses in Mice

by Yujun Liu, Hao Gong, Jiaming Zhu and Fenyong Liu

Vaccines 2026, 14(3), 279; https://doi.org/10.3390/vaccines14030279 - 22 Mar 2026

Viewed by 367

Abstract

Background: Oral gene delivery vectors, such as those derived from attenuated Salmonella strains, have shown great promise in oral vaccine development against various human diseases. Human cytomegalovirus (CMV) is a herpesvirus capable of affecting the global population and establishing lifelong infection. Generation of [...] Read more.

Background: Oral gene delivery vectors, such as those derived from attenuated Salmonella strains, have shown great promise in oral vaccine development against various human diseases. Human cytomegalovirus (CMV) is a herpesvirus capable of affecting the global population and establishing lifelong infection. Generation of an anti-CMV vaccine is a major public health priority. Methods: This study reports the development of a novel weakened Salmonella strain, S713, and the effects of this strain as an oral vaccine candidate against murine cytomegalovirus (MCMV) infection in mice. Results: The weakened Salmonella strain S713 was attenuated in killing mice in vivo by >500,000 fold compared to a clinical strain, following intragastric instillation in animals. Mice intragastrically immunized with S713 that produced MCMV M24 protein exhibited elevated anti-MCMV mucosal IgA and serum IgG titers and enhanced anti-MCMV T cell responses. Moreover, immunization with the generated vaccine in MCMV-challenged mice not only suppressed viral replication in lungs, spleens, livers, and salivary glands but also increased animal survival. Conclusions: These findings demonstrate strong and effective anti-MCMV immune responses induced by the generated M24-expressing vaccine. Furthermore, our results reveal the promising capability of weakened strain S713 expressing different CMV proteins to act as oral vaccines against CMV infections and diseases. Full article

(This article belongs to the Special Issue Oral and Nucleic Acid Vaccines for Zoonotic and Animal Infectious Diseases)

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17 pages, 1852 KB

Open AccessArticle

Development and Validation of Sixplexed Opsonophagocytic Killing Assay for Serotype-Specific Functional Pneumococcal Antibody Measurement

by A-Yeung Jang, Hyun Jung Ji, Yu Jung Choi, Eliel Nham, Jin Gu Yoon, Min Joo Choi, Ji Yun Noh, Hee Jin Cheong, Ho Seong Seo and Joon Young Song

Vaccines 2026, 14(3), 278; https://doi.org/10.3390/vaccines14030278 - 21 Mar 2026

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Abstract

Background: Although pneumococcal conjugate vaccines (PCVs) have substantially reduced invasive pneumococcal disease, the emergence of non-vaccine serotypes and antimicrobial-resistant strains has driven the development of higher-valency vaccines. To support functional immune evaluation of these vaccines, we developed and validated a sixplexed opsonophagocytic [...] Read more.

Background: Although pneumococcal conjugate vaccines (PCVs) have substantially reduced invasive pneumococcal disease, the emergence of non-vaccine serotypes and antimicrobial-resistant strains has driven the development of higher-valency vaccines. To support functional immune evaluation of these vaccines, we developed and validated a sixplexed opsonophagocytic killing assay (OPA) covering 24 pneumococcal serotypes. Methods: Eight additional serotypes, beyond the 16 included in the conventional fourplex OPA, were generated through stepwise natural mutation under increasing concentrations of ciprofloxacin or doxycycline. Assay conditions were optimized by evaluating multiple effector-to-target (E:T) ratios and baby rabbit complement (BRC) concentrations to minimize non-specific killing (NSK). Validation assessed (1) specificity using inhibition OPA with homologous and heterologous polysaccharides, (2) accuracy by comparison with the single-serotype OPA (SOPA), and (3) precision across five independent experiments using the coefficient of variation (CV). Results: An E:T ratio of 200:1 combined with 10% BRC consistently maintained NSK below 30% across all assay sets. High serotype specificity was demonstrated by near-complete inhibition following homologous polysaccharide adsorption for all serotypes except serotypes 4 and 8, which exhibited very low opsonic indices. Results from the sixplexed OPA showed strong concordance with SOPA, and overall assay precision was acceptable, with CVs generally below 30% when serotypes with very low opsonic activity were excluded. Conclusions: The sixplexed OPA expands functional antibody assessment from 16 to 24 serotypes within four assay sets, providing an efficient and scalable platform for immunogenicity evaluation of current and next-generation high-valency pneumococcal vaccines. Full article

(This article belongs to the Special Issue Advances in Vaccines Against Infectious Diseases)

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25 pages, 1150 KB

Open AccessReview

Recent Advances, Bottlenecks, and Future Directions in Plasmodium falciparum Vaccine Development

by Gulbuse Turan, Maxence J. Boggio, Ahmad Syibli Othman, Victory Nnaemeka, Adrian V. S. Hill and Ahmed M. Salman

Vaccines 2026, 14(3), 277; https://doi.org/10.3390/vaccines14030277 - 21 Mar 2026

Viewed by 812

Abstract

Malaria remains a major global health burden, with an estimated 282 million cases and 610,000 deaths reported in 2024, disproportionately affecting children under five years of age and pregnant women in sub-Saharan Africa. Although antimalarial drugs are highly effective at clearing infections, their [...] Read more.

Malaria remains a major global health burden, with an estimated 282 million cases and 610,000 deaths reported in 2024, disproportionately affecting children under five years of age and pregnant women in sub-Saharan Africa. Although antimalarial drugs are highly effective at clearing infections, their reliance on timely diagnosis and treatment limits their scalability as a population-wide control strategy. Vaccines therefore represent a critical tool for reducing malaria-associated morbidity and mortality, as well as interrupting parasite transmission, by inducing durable protective immunity. However, the complex lifecycle of Plasmodium parasites poses significant challenges for vaccine development, including the identification of protective antigens and optimal vaccine formulations. In this review, we summarize current vaccine strategies and discuss their key limitations. We also highlight emerging opportunities for possible avenues for future research and development. Full article

(This article belongs to the Special Issue Recent Advances in Malaria Vaccine Development—2nd Edition)

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20 pages, 5021 KB

Open AccessArticle

Dissolvable Microneedle Delivery of a Replication-Deficient Orthopoxvirus Vaccine: Formulation Screening and Immunogenicity Evaluation for Monkeypox Prevention

by Bin Wang, Kehui Wang, Zhiyao Xu, Weihua Liu, Xianhuang Li, Linhao Li, Renhui Zhou, Xingyue Du, Jin Jin, Yaqing Xu, Rihui Qin, Xiong Liu, Dayang Zou and Wei Liu

Vaccines 2026, 14(3), 276; https://doi.org/10.3390/vaccines14030276 - 20 Mar 2026

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Abstract

Background: The global spread of monkeypox virus (MPXV) highlights an urgent need for thermostable and easily administrable vaccines. Current orthopoxvirus vaccines are limited by cold-chain dependence and inconvenient injection-based delivery. Objectives: This study aimed to develop a dissolvable microneedle (DMN) vaccine against monkeypox [...] Read more.

Background: The global spread of monkeypox virus (MPXV) highlights an urgent need for thermostable and easily administrable vaccines. Current orthopoxvirus vaccines are limited by cold-chain dependence and inconvenient injection-based delivery. Objectives: This study aimed to develop a dissolvable microneedle (DMN) vaccine against monkeypox based on a replication-deficient orthopoxvirus platform, through systematic formulation screening, stabilization mechanism exploration, and rigorous in vivo immunogenicity evaluation. Methods: A film-based approach was adopted for efficient, high-throughput formulation screening and thermostability assessment. NTV was mixed with excipients and dried into solid films. Stability was monitored via RT-qPCR after storage at 4 °C to 40 °C. The lead formulation was physically characterized, then used to fabricate MVA-BN-loaded DMN patches, which were further evaluated for in vivo immunogenicity via immunization in BALB/c mice. Results: The optimal formulation F2 (containing dextran, L-threonine, and BSA/HSA) showed a potency loss of only ~1 log₁₀ after 2 months at 25 °C, and <1 log₁₀ loss after 1 week at 37 °C. SEM revealed a porous virus-entrapment morphology, and FTIR indicated enhanced hydrogen bonding between the virus and the dextran matrix. The formulation was successfully manufactured into DMNs that dissolved within 5 min. In mice, these DMNs elicited robust MPXV-specific IgG and neutralizing antibody responses, with immunogenicity comparable to that induced by conventional intramuscular injection. Conclusions: This study successfully established a thermostable formulation and dissolvable microneedle delivery platform for replication-deficient orthopoxvirus vaccines against monkeypox. The optimized DMN vaccine induced robust MPXV-specific immune responses in mice with immunogenicity comparable to intramuscular injection, addressing the core limitations of current vaccines and providing a promising solution for monkeypox prevention. Full article

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

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14 pages, 3007 KB

Open AccessArticle

Generation and Evaluation of a Multi-Epitope Vaccine Against Acinetobacter baumannii, a Nosocomial Bacterial Pathogen

by Nicolas D. Prather, Jadelynn Aki, Sean Jeffreys, Bernard P. Arulanandam, Chiung-Yu Hung and Jieh-Juen Yu

Vaccines 2026, 14(3), 275; https://doi.org/10.3390/vaccines14030275 - 20 Mar 2026

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Abstract

Background/Objectives: Multidrug-resistant (MDR) Acinetobacter baumannii (Ab) has emerged as a significant bacterial pathogen responsible for nosocomial infections. The most common clinical manifestations of Ab infection include ventilator-associated pneumonia and catheter-related bloodstream/urinary infections. Given the extensive MDR phenotype of Ab, preventive [...] Read more.

Background/Objectives: Multidrug-resistant (MDR) Acinetobacter baumannii (Ab) has emerged as a significant bacterial pathogen responsible for nosocomial infections. The most common clinical manifestations of Ab infection include ventilator-associated pneumonia and catheter-related bloodstream/urinary infections. Given the extensive MDR phenotype of Ab, preventive vaccination strategies are crucial for protecting susceptible populations. Methods: We utilized immunoinformatics to identify candidate peptides containing both putative B- and T-cell epitopes from proteins associated with Ab pathogenesis. Subsequently, we designed novel Acinetobacter Multi-Epitope Vaccines (AMEVs), each comprising an Ab thioredoxin A (TrxA) leader protein, five to seven of the identified peptide antigens, and a C-terminal His(6x)-tag to facilitate protein purification. Results: Subcutaneous vaccination of C57BL/6 mice with AMEV1 or AMEV2, formulated with TiterMax adjuvant, conferred 60% and 80% protection, respectively, against intraperitoneal Ab challenge. AMEV vaccination induced a robust antibody response to each corresponding whole protein and most of its component peptides. We then constructed an improved vaccine, AMEV5, which included the Ab TrxA protein and seven confirmed B-cell epitope peptides. Subcutaneous immunization of BALB/c mice (n = 10 per group) with rAMEV5 emulsified in Adda03 adjuvant activated antigen-specific IL-5-secreting T cells and antibody-producing B cells. Evaluation of vaccine efficacy demonstrated that AMEV2- and AMEV5-immunized mice were protected from a lethal intraperitoneal Ab challenge, with survival rates of 70% and 90%, respectively. Conclusions: These study results provide insights into the application of reverse vaccinology to combat the rise of MDR Acinetobacter infection. Full article

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

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18 pages, 461 KB

Open AccessArticle

Examining Discordance in Perceptions of COVID-19 and Influenza Vaccine Safety During Pregnancy Among a Cohort of US Adults

by Rachael Piltch-Loeb, Bai Xi Jasmine Chan, Josefina Nuñez Sahr, Chloe Teasdale, Sasha Fleary, Kate Penrose, Jenna Sanborn, Subha Balasubramanian, McKaylee Robertson and Angela Parcesepe

Vaccines 2026, 14(3), 274; https://doi.org/10.3390/vaccines14030274 - 20 Mar 2026

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Abstract

Background/Objectives: Vaccination is an important strategy to protect pregnant people, fetuses, and infants from severe influenza and COVID-19. However, as of April 2025 in the United States, only 14% of pregnant women had received the 2024–2025 COVID-19 vaccine, while influenza vaccine uptake among [...] Read more.

Background/Objectives: Vaccination is an important strategy to protect pregnant people, fetuses, and infants from severe influenza and COVID-19. However, as of April 2025 in the United States, only 14% of pregnant women had received the 2024–2025 COVID-19 vaccine, while influenza vaccine uptake among pregnant women was 38% compared to 57% in 2020. Our study assessed the perceived safety of receiving these vaccines during pregnancy within a community-based national cohort. Methods: Participants reported safety perceptions of vaccination during pregnancy and were categorized as (1) endorsing the safety of both COVID-19 and influenza vaccines, (2) endorsing the safety of only the influenza vaccine, (3) endorsing the safety of only the COVID-19 vaccine and (4) endorsing the safety of neither vaccine during pregnancy. We examined sociodemographics, behaviors, and beliefs correlated with these four categories. Log-binomial models were used to estimate the prevalence ratios of (a) endorsing the safety of only influenza vaccine versus endorsing the safety of both COVID-19 and influenza vaccines during pregnancy, and (b) endorsing safety of neither versus both vaccines during pregnancy. Results: In total, 40% of adults (N = 1725) endorsed the safety of both vaccines during pregnancy, 18% (N = 751) endorsed the safety of only the influenza vaccine, 4% (N = 183) endorsed the safety of only the COVID-19 vaccine, and 38% (N = 1621) did not endorse the safety of either vaccine during pregnancy. Participants who were non-Hispanic Black, reported inconsistent vaccination habits, and expressed low trust in government and healthcare providers were more likely to endorse the safety of only the influenza vaccine or neither vaccine compared with endorsing both vaccines. Conclusions: These findings highlight the need to build trust in the medical system, reduce access barriers, and use equitable, community-driven messaging to strengthen confidence in the safety of receiving the COVID-19 and influenza vaccines during pregnancy. Full article

(This article belongs to the Special Issue Advancing Health: Vaccination and Infectious Disease Prevention in Pregnant Women, Neonates, Infants, and Children)

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20 pages, 1417 KB

Open AccessArticle

Rational Design of a Chimpanzee Adenoviral-Vector Vaccine Against Yellow Fever Through the Modification of Antigen Transmembrane Domains

by Marta Ulaszewska, Ji Ma, Susan J. Morris, Sophie M. Jegouic Goodall, Winnie Kerstens, Hendrik Jan Thibaut, Lotte Coelmont, Kai Dallmeier, Sarah C. Gilbert and Barbara Dema

Vaccines 2026, 14(3), 273; https://doi.org/10.3390/vaccines14030273 - 20 Mar 2026

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Abstract

Background/Objectives: Chimpanzee adenoviral-vectored vaccines have proven to be both safe and effective, with a manufacturing and distribution pipeline capable of rapid global supply, as demonstrated during the COVID-19 pandemic. Yellow fever is a mosquito-borne viral hemorrhagic disease endemic in parts of Africa [...] Read more.

Background/Objectives: Chimpanzee adenoviral-vectored vaccines have proven to be both safe and effective, with a manufacturing and distribution pipeline capable of rapid global supply, as demonstrated during the COVID-19 pandemic. Yellow fever is a mosquito-borne viral hemorrhagic disease endemic in parts of Africa and Latin America, and although an effective live attenuated vaccine exists, its use is limited by safety and eligibility restrictions. Moreover, large outbreaks continue to expose critical challenges, such as an insufficient vaccine supply, reliance on fractional dosing, and slow and difficult-to-scale manufacturing processes. Here, we report the design, development and in vivo immunogenicity of multiple yellow fever virus (YFV) antigen constructs based on the pre-membrane (prM) and envelope (E) proteins—with or without the transmembrane domain (TM or ΔTM)—delivered using the ChAdOx1 adenoviral vector. Methods: Four ChAdOx1 YF vaccines were developed, and immunogenicity was evaluated. The efficacy of the full-length YF envelope vaccine was also tested in Balb/c mice. Results/Conclusions: In contrast to previously described orthoflavivirus vaccines on the same platform, the full-length antigen elicited superior immunogenicity and conferred protection against intracranial challenge with the YF17D virus in mice. Notably, this protection was comparable to that induced by the licensed YF17D vaccine, highlighting the promise of this platform as a next-generation yellow fever vaccine candidate. Full article

(This article belongs to the Special Issue Vaccines Against Flaviviruses and Alphaviruses: Recent Advances and Future Challenges—2nd Edition)

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14 pages, 539 KB

Open AccessArticle

The Status of Measles and Rubella Outbreak Detection, Early Alerts, and Response in Eastern Mediterranean Region (EMR), 2023

by Eman Elmahdy, Eltayeb Elfakki, Amany Ghoniem, Basma M. Saleh, Frank Mahony and Quamrul Hasan

Vaccines 2026, 14(3), 272; https://doi.org/10.3390/vaccines14030272 - 20 Mar 2026

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Abstract

Background: Measles and rubella remain major public health concerns in the Eastern Mediterranean Region (EMR), despite regional elimination goals. In 2023, the region experienced an increase in measles outbreaks. This study assessed outbreak detection and response challenges in either case definition or [...] Read more.

Background: Measles and rubella remain major public health concerns in the Eastern Mediterranean Region (EMR), despite regional elimination goals. In 2023, the region experienced an increase in measles outbreaks. This study assessed outbreak detection and response challenges in either case definition or data analysis, in addition to gaps in laboratory and genotyping data integration to improve preparedness and response. Method: A retrospective epidemiological study was conducted using official World Health Organization (WHO) data on measles and rubella (MR) in EMR countries, from 1 January to 31 December 2023. Routine MR surveillance line list, genotyping data and supplemental immunization activity (SIA) reported by countries were used. Results: In 2023, 1206 suspected measles outbreaks were reported in 13 countries; 942 (78%) were confirmed. Rubella accounted for 158 confirmed outbreaks. Children under 5 years old comprised 76% of cases, with 62% zero dose. Timely detection was achieved in only 46% of outbreaks, with wide national variation. Genotype B3 predominated, but missing genotyping data limited verification. Six immunization campaigns occurred; however, outbreaks persisted due to high zero dose, limited targeting, and delayed responses. Conclusions: Persistent immunity gaps, under detection, inconsistent genotyping, and delayed response hindered MR control in EMR. Strengthening surveillance, integrating epidemiological and molecular data, expanding targeted supplementary immunization activities, and ensuring timely response are essential tasks. Standardized outbreak definitions, capacity building, and regular subnational analyses remain critical to regional elimination goals. Full article

(This article belongs to the Special Issue Vaccines and Immunization: Measles, Mumps, and Rubella)

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9 pages, 324 KB

Open AccessBrief Report

Impact of the COVID-19 Pandemic on Routine Childhood Vaccination in Oklahoma

by Jessica Beetch, Laura A. Beebe, Amanda Janitz, Chao Xu, Mary Gowin and Katrin Gaardbo Kuhn

Vaccines 2026, 14(3), 271; https://doi.org/10.3390/vaccines14030271 - 19 Mar 2026

Viewed by 416

Abstract

Background/Objectives: The COVID-19 pandemic substantially disrupted routine childhood vaccination practices across the United States. Oklahoma, a state characterized by lower socioeconomic indicators and higher levels of vaccine hesitancy, may have been particularly vulnerable to these disruptions. This study aimed to assess the [...] Read more.

Background/Objectives: The COVID-19 pandemic substantially disrupted routine childhood vaccination practices across the United States. Oklahoma, a state characterized by lower socioeconomic indicators and higher levels of vaccine hesitancy, may have been particularly vulnerable to these disruptions. This study aimed to assess the impact of the COVID-19 pandemic on routine childhood vaccination in Oklahoma. Methods: Data were obtained from the Oklahoma State Immunization Information System to examine changes in the administration of DTaP and MMR vaccines before and during the COVID-19 pandemic, stratified by pandemic phase. Percentage changes in vaccine doses administered were calculated across time periods. Log-binomial regression models were used to evaluate the association between pandemic timing and receipt of subsequent DTaP doses among children under one year of age. Results: Administration of both DTaP and MMR vaccines declined during the COVID-19 pandemic across all pandemic phases examined. Compared with the pre-pandemic period, fewer children returned for subsequent DTaP doses during the pandemic. Regression analyses indicated a reduced likelihood of completing age-appropriate DTaP dosing among infants during the pandemic. Conclusions: Routine childhood vaccination in Oklahoma declined during the COVID-19 pandemic, with persistent reductions observed across pandemic phases. These findings highlight vulnerabilities in vaccination delivery during public health emergencies and underscore the need for targeted state-level strategies to sustain routine immunization services during future crises. Full article

(This article belongs to the Section Epidemiology and Vaccination)

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4 pages, 157 KB

Open AccessEditorial

Preventing Human Papillomavirus and Vaccine Strategies

by Rui M. Gil da Costa

Vaccines 2026, 14(3), 270; https://doi.org/10.3390/vaccines14030270 - 18 Mar 2026

Viewed by 497

Abstract

Vaccination against human papillomavirus (HPV) has been widely adopted, aiming at preventing infection and, ultimately, the development of HPV-driven uterine cervical neoplasia [...] Full article

(This article belongs to the Special Issue Prevention of Human Papillomavirus and Vaccines Strategies)

13 pages, 1752 KB

Open AccessArticle

Prophylactic HPV Vaccination in Gynaecological Practice: Recommendations, Practices, and Challenges Reported in the ESGO-PERCH HPV Survey

by Joanna Kacperczyk-Bartnik, Marc Arbyn, Sophie Denoël, Esra Bilir, Nina Dhollander, Zoia Razumova, Khayal Gasimli, Andrej Cokan, Houssein El Hajj, Tibor Andrea Zwimpfer, Maria Kyrgiou, Murat Gultekin and Nicolò Bizzarri

Vaccines 2026, 14(3), 269; https://doi.org/10.3390/vaccines14030269 - 16 Mar 2026

Viewed by 757

Abstract

Background/Objectives: HPV vaccination is highly effective in preventing HPV-related cancers when administered before viral exposure. However, vaccination practices for patients already diagnosed with gynaecological cancers remain poorly characterized. Understanding clinicians’ perspectives and barriers is essential for optimizing preventive strategies in oncologic care. Methods: [...] Read more.

Background/Objectives: HPV vaccination is highly effective in preventing HPV-related cancers when administered before viral exposure. However, vaccination practices for patients already diagnosed with gynaecological cancers remain poorly characterized. Understanding clinicians’ perspectives and barriers is essential for optimizing preventive strategies in oncologic care. Methods: We conducted an international, web-based survey among members of the European Society of Gynaecological Oncology (ESGO) and the European Network of Young Gynaecological Oncologists (ENYGO). The questionnaire explored clinicians’ attitudes, practices, and perceived obstacles regarding HPV vaccination in patients with gynaecological cancer or pre-invasive disease across multiple clinical scenarios and age groups. Results: A total of 149 respondents from 33 countries completed the survey. Most clinicians supported HPV vaccination for patients treated for cervical precancer (78–82% for patients under 45 years), and even for invasive cervical cancer (57–62%). Recommendations varied by patients’ age, cancer type, and treatment status. For endometrial and ovarian cancer, endorsement ranged from 16% to 53%, depending on patient age. Timing of vaccination was a point of divergence: some clinicians favoured vaccination immediately after treatment for CIN2+, while others recommended delaying vaccination depending on HPV test results. Reported barriers discouraging HPV vaccination recommendations included misinformation (69.8%), lack of patient education materials (52.3%), and time constraints (48.3%), alongside economic factors and uncertainty about efficacy in oncologic settings. Conclusions: The survey shows that HPV vaccination is often recommended beyond evidence-supported indications. Randomized trials have not demonstrated a reduction in CIN2+ recurrence with adjuvant vaccination, and no evidence supports vaccination in women with invasive gynaecological cancers. These findings reveal a gap between clinical practice and available evidence, highlighting the need for clearer, evidence-based guidance. Full article

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

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27 pages, 1742 KB

Open AccessReview

How to Employ Trained Immunity and Trained Immunity-Based Vaccines to Inhibit Allergic Inflammation

by Wonho Kim and Dooil Jeoung

Vaccines 2026, 14(3), 268; https://doi.org/10.3390/vaccines14030268 - 16 Mar 2026

Viewed by 757

Abstract

Trained immunity confers protection against subsequent unrelated infections through metabolic and epigenetic reprogramming. Unlike adaptive immunity, trained innate immunity provides broad, non-specific protection against diverse heterologous pathogens. In addition to potentiating inflammatory responses upon secondary challenge, trained innate immune cells can also acquire [...] Read more.

Trained immunity confers protection against subsequent unrelated infections through metabolic and epigenetic reprogramming. Unlike adaptive immunity, trained innate immunity provides broad, non-specific protection against diverse heterologous pathogens. In addition to potentiating inflammatory responses upon secondary challenge, trained innate immune cells can also acquire anti-inflammatory and tolerogenic phenotypes, a property with important implications for chronic inflammatory diseases such as allergic disorders. Trained immunity-based vaccines (TIbVs) have emerged as promising immunomodulatory strategies capable of attenuating allergic inflammation by inducing immune tolerance. Similarly, allergen-specific immunotherapy (AIT) promotes long-term tolerance to allergens through metabolic and epigenetic reprogramming of innate immune cells. AIT drives the differentiation of monocytes into tolerogenic dendritic cells, thereby reshaping downstream adaptive immune responses. This review summarizes the current understanding of trained immunity and its role in protection against the same and heterologous infections. We discuss the molecular mechanisms underlying trained immunity, with an emphasis on metabolic and epigenetic reprogramming. Furthermore, we highlight the therapeutic potential of TIbVs and AIT as next-generation vaccines for allergic diseases. A deeper understanding of AIT-induced immune tolerance, the identification of predictive biomarkers, and the optimization of delivery platforms—such as lipid nanoparticle-based systems—will be critical for improving the safety and efficacy of future anti-allergy vaccines. Full article

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

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19 pages, 681 KB

Open AccessReview

Oropouche Virus (OROV) Vaccine Development for Vulnerable Populations: Epidemiological Context, Challenges and Future Directions

by Wenrui Wu and Yiu-Wing Kam

Vaccines 2026, 14(3), 267; https://doi.org/10.3390/vaccines14030267 - 16 Mar 2026

Viewed by 666

Abstract

Oropouche virus (OROV) is an emerging arthropod-borne virus in the Americas that has evolved from a pathogen historically restricted to forest environments into an increasingly important regional and international public health concern. Despite decades of documented circulation, the true burden of OROV infection [...] Read more.

Oropouche virus (OROV) is an emerging arthropod-borne virus in the Americas that has evolved from a pathogen historically restricted to forest environments into an increasingly important regional and international public health concern. Despite decades of documented circulation, the true burden of OROV infection remains substantially underestimated, largely because of frequent misdiagnosis and the high proportion of asymptomatic or subclinical infections. This review synthesizes current evidence on the historical emergence, epidemiology, transmission dynamics, and clinical features of OROV, with a particular focus on populations at increased risk due to biological susceptibility, environmental exposure, and limited access to healthcare. Drawing on seroepidemiological data, we demonstrate that OROV transmission is far more widespread than routine surveillance suggests and examine how factors such as age, pregnancy, immune status, underlying health conditions, occupational exposure, and healthcare accessibility interact to influence disease risk and detection. Although multiple vaccine platforms have shown promise in preclinical studies, progress toward clinical development remains constrained by limited immunological evidence, shortcomings of available animal models, diagnostic uncertainty, and structural barriers in endemic regions. We propose that future OROV vaccine development prioritize population-specific needs rather than focusing solely on technological platforms, and that effective prevention will require integrating vaccination with strengthened surveillance, improved diagnostics, and equitable delivery systems. Full article

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

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22 pages, 2299 KB

Open AccessArticle

Protein Priming Followed by a Replication-Competent VSV-GP Vector Boost Induces Sustained Immune Control in Therapeutic Hepatitis B Vaccination

by Jinpeng Su, Anna D. Kosinska, Susanne Miko, Edanur Ates Öz, Dorothee von Laer, Janine Kimpel and Ulrike Protzer

Vaccines 2026, 14(3), 266; https://doi.org/10.3390/vaccines14030266 - 16 Mar 2026

Viewed by 540

Abstract

Background/Objectives: Eliciting robust immune responses against the hepatitis B virus (HBV) through therapeutic vaccination holds promise for curing chronic hepatitis B. We previously developed the heterologous protein prime/viral vector boost clinical vaccine candidate, TherVacB. Here, we evaluated a replication-competent chimeric vesicular [...] Read more.

Background/Objectives: Eliciting robust immune responses against the hepatitis B virus (HBV) through therapeutic vaccination holds promise for curing chronic hepatitis B. We previously developed the heterologous protein prime/viral vector boost clinical vaccine candidate, TherVacB. Here, we evaluated a replication-competent chimeric vesicular stomatitis virus vector (VSV-GP) as an alternative viral vector boost vaccine. Methods: A recombinant VSV-GP vector co-expressing HBV surface and core antigens (VSV-GP-HBs/c) was generated and characterized for antigen expression. Its immunogenicity, antiviral efficacy, and durability were assessed in HBV-naïve and HBV-carrier mice, using protein primed, viral vector-primed, and multi-viral vector boost regimens. Results: VSV-GP-HBs/c efficiently expressed both HBV antigens in vitro. A single immunization with VSV-GP-HBs/c induced only weak HBV-specific immune responses in vivo. Replacing protein priming with VSV-GP-HBs/c resulted in modest immune activation and limited antiviral effects in HBV-carrier mice. In contrast, substituting the modified vaccinia virus Ankara (MVA)-HBs/c boost in the TherVacB regimen with VSV-GP-HBs/c elicited robust HBV-specific antibody responses and strong CD4 and CD8 T-cell immunity, assessed by intracellular IFN-γ staining after peptide stimulation. This regimen achieved a substantial reduction in serum HBsAg levels, numbers of HBV-positive hepatocytes, and intrahepatic HBV-DNA, with antiviral efficacy comparable to that of the classical TherVacB regimen. Notably, a second viral vector boost did not enhance HBV-specific immunity or antiviral efficacy; instead, it promoted dominant vector-specific CD8 T-cell responses. Long-term analyses performed 10 weeks after the last vaccination further demonstrated that a single protein-prime/VSV-GP-HBs/c boost was sufficient to achieve sustained antiviral control. Conclusions: These findings identify VSV-GP-HBs/c as an effective boost vector for therapeutic hepatitis B vaccination and establish protein priming followed by a single viral vector boost as an optimal strategy for sustained antiviral immunity. Full article

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

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14 pages, 1468 KB

Open AccessArticle

CHO Cell-Produced Truncated Bovine Ephemeral Fever Virus Glycoprotein as a Promising Subunit Vaccine Candidate for Cattle

by Huan-Yu Hsu, Shu-Ju Yeh, Chi-Chih Chen and Guan-Ming Ke

Vaccines 2026, 14(3), 265; https://doi.org/10.3390/vaccines14030265 - 15 Mar 2026

Viewed by 531

Abstract

Background/Objectives: Bovine ephemeral fever (BEF) is a significant disease affecting the cattle industry. The current control strategy for BEF in the field primarily relies on inactivated vaccines. However, some individuals have experienced hypersensitive reactions to these vaccines, prompting the exploration of subunit vaccines [...] Read more.

Background/Objectives: Bovine ephemeral fever (BEF) is a significant disease affecting the cattle industry. The current control strategy for BEF in the field primarily relies on inactivated vaccines. However, some individuals have experienced hypersensitive reactions to these vaccines, prompting the exploration of subunit vaccines as a potential alternative for BEF prevention. Glycoprotein (G protein)-based subunit vaccines derived from virions have successfully induced neutralizing antibodies in cattle for over a decade. Nevertheless, the lack of recent studies evaluating their efficacy using recombinant proteins has raised concerns regarding the development of BEF subunit vaccines for practical field application. Therefore, the objective of this study was to evaluate the antigenicity of a novel truncated G protein produced in mammalian cells as a candidate subunit vaccine for BEF in cattle. Methods: In this study, the G protein with full ectodomain and a version truncated at the C-terminal domain were successfully generated using the ExpiCHO™ expression system. Vaccine efficacy was evaluated weekly by measuring neutralizing antibody titers and cytokine mRNA expression levels following vaccination. Results: Results show that the recombinant protein s510, derived from the G protein of BEF, can stimulate cattle to produce an average 35-fold increase in neutralizing antibodies after three doses of vaccination. The significant upregulation of IFN-γ mRNA supports the effectiveness of the s510-based subunit vaccine and indicates the activation of a cytotoxic immune response in cattle following vaccination. Conclusions: In conclusion, the results indicate that the recombinant protein s510 is a promising antigen for future BEF subunit vaccine development in this study. Full article

(This article belongs to the Special Issue Animal Vaccines: 2nd Edition)

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16 pages, 570 KB

Open AccessArticle

Routine DTP Vaccination Coverage and Herd Immunity Against Pertussis in 2024 Did Not Recover to Pre-COVID-19 Levels Globally and in WHO Regions

by Pedro Plans-Rubió

Vaccines 2026, 14(3), 264; https://doi.org/10.3390/vaccines14030264 - 13 Mar 2026

Viewed by 615

Abstract

Objectives: The study’s objective was to assess ten diphtheria–tetanus–pertussis (DTP) vaccination program indicators globally and in World Health Organization (WHO) regions in 2024, and compare the values in 2024 and 2019. Methods: Global and regional values for routine DTP vaccination performance [...] Read more.

Objectives: The study’s objective was to assess ten diphtheria–tetanus–pertussis (DTP) vaccination program indicators globally and in World Health Organization (WHO) regions in 2024, and compare the values in 2024 and 2019. Methods: Global and regional values for routine DTP vaccination performance indicators were assessed in 2024. Means and percentages in 2024 and 2019 were compared using the t-test and Chi-square test, respectively, considering p < 0.05 as statistically significant. High-priority countries for DTP vaccination coverage increase were identified in each WHO region based on the indicators assessed in this study. Results: The global mean vaccination coverage for DTP1, DTP3 and three DTP doses were 90.7%, 86.6% and 72.8%, respectively, in 2024. Eight of the ten indicators assessed in this study worsened and two improved globally from 2019 to 2024. The differences between 2019 and 2024 were statistically significant for the three-dose DTP coverage decrease in the European WHO region (88.1% vs. 82.5%, p < 0.05), and the decrease in the global percentage of countries with ≥90% three-dose coverage (34% vs. 21%, OR = 0.52, 95% CI: 0.33–0.81, p < 0.005). This study identified 27 (13.8%) high-priority countries for DTP vaccination coverage increase due to DTP1 coverage lower than 80%; 47 (24.1%) countries due to DTP3 coverage lower than 80%; and 48 (24.6%) countries due to three-dose coverage lower than 60%. Conclusions: Global and regional DTP vaccination performance indicators in 2024 did not recover to pre-pandemic levels, although the differences between 2024 and 2019 were statistically significant only for two regional indicators. Full article

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

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14 pages, 2029 KB

Open AccessArticle

Evaluation of an Effective Intradermal Foot-and-Mouth Disease Vaccine for Early Protection

by Dong-Wan Kim, Seo-Yong Lee, Tae-Jun Kim, Hyejin Kim, Ji-Hyeon Hwang, Sun Young Park, Young-Joon Ko, Yoon-Hee Lee, Jong-Hyeon Park and Sung-Han Park

Vaccines 2026, 14(3), 263; https://doi.org/10.3390/vaccines14030263 - 13 Mar 2026

Viewed by 606

Abstract

Background: In South Korea, foot-and-mouth disease (FMD), a highly contagious viral infection that affects cloven-hoofed animals, has led to the implementation of a bivalent FMD vaccination program. The current FMD vaccination strategy involves intramuscular (IM) administration to the shoulder region of the swine. [...] Read more.

Background: In South Korea, foot-and-mouth disease (FMD), a highly contagious viral infection that affects cloven-hoofed animals, has led to the implementation of a bivalent FMD vaccination program. The current FMD vaccination strategy involves intramuscular (IM) administration to the shoulder region of the swine. However, this method is associated with adverse reactions at injection sites. Our previous studies have demonstrated that intradermal (ID) vaccination eliminates these side effects while maintaining immunogenicity comparable to that of IM vaccination. This study aimed to assess the early immune response induced by ID vaccination and compare its protective ability against FMDV serotype O with that of a commercial IM vaccine recently used in South Korea. Methods: An ID FMD vaccine was evaluated using two adjuvants, ISA 207 (50%) and EMULSIGEN-D (15%). Virus neutralization (VN) titers and structural protein levels were measured to compare efficacy across groups. To assess the early protective efficacy of ID vaccination, viral challenge experiments were conducted at 7 and 14 days post-vaccination (dpv). Results: Swine vaccinated via the ID route exhibited no clinical symptoms at 14 dpv, indicating effective early protection against FMD (O/AS/SKR/2019). In addition, no side effects of FMD ID vaccination were observed. Conclusions: These results suggest that ID vaccination could serve as a viable alternative to conventional IM vaccination, which is frequently associated with adverse effects. Importantly, this study demonstrates that ID vaccination can provide effective early protection within 7–14 days post-vaccination, highlighting its potential utility for emergency outbreak control. Full article

(This article belongs to the Section Veterinary Vaccines)

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15 pages, 2652 KB

Open AccessArticle

From Estimated Targets to Verified Coverage: Implementation of a Community Health Worker-Based Tracking Intervention to Address Denominator Inaccuracies in High-Risk Urban Settings of Balochistan, Pakistan

by Rubab Kamran, Maliha Fatima, Babar Shahid, Muhammad Ayaz, Farid Ullah Khan, Simran Siraj, Zainab Farid, Noshad Ali, Ali Turab, Soofia Yunus, Zaffar Iqbal and M. Imran Khan

Vaccines 2026, 14(3), 262; https://doi.org/10.3390/vaccines14030262 - 13 Mar 2026

Viewed by 716

Abstract

Background: Routine immunization programs in Pakistan rely heavily on estimated population denominators, limiting accurate identification and follow-up of zero-dose and under-immunized children, particularly in high-risk urban settings such as Quetta, Balochistan. Methods: A quasi-experimental, pre–post implementation study was conducted from June [...] Read more.

Background: Routine immunization programs in Pakistan rely heavily on estimated population denominators, limiting accurate identification and follow-up of zero-dose and under-immunized children, particularly in high-risk urban settings such as Quetta, Balochistan. Methods: A quasi-experimental, pre–post implementation study was conducted from June 2024 to June 2025 across three low-performing union councils. A CHW-based household tracking tool was integrated within existing PEI–EPI systems. Data were derived from CHW Books, Rapid Convenience Assessments (RCA), and routine MIS reports. Descriptive statistical analysis was employed to assess trends in immunization coverage and program performance; no inferential statistical tests were applied due to the use of complete programmatic (census-based) data rather than sampled observations. Results: Antigen-specific coverage improved substantially, with Penta-3 coverage increasing from 22% to 95%, zero-dose conversion from 45% to 65%, and defaulter follow-up from 14% to 79%. All three union councils transitioned to Category 1 operational status. Administrative coverage exceeding 100%, reflecting population-level coverage and denominator correction rather than true population-level coverage. Conclusions: Integrating CHW-based tracking with dynamic denominator verification enhances routine immunization, microplanning, equity, and operational performance in high-risk LMIC urban settings. Full article

(This article belongs to the Special Issue Effectiveness and Safety of Vaccines in Special Populations)

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28 pages, 5469 KB

Open AccessArticle

In Silico Design and Subsequent Expression of Human Papillomavirus-16 and -18 L1 Vaccine Antigens in Broccoli

by Neelam Batool, Khadeeja Ahsan, Kainat Qadeer, Al Fajar, Alveena Farid, Muhammad Sameeullah, Fatima Ijaz, Muhammad Suleman Malik, Fizza Ahmad Tariq, Andreas Günter Lössl, Martin Müller and Mohammad Tahir Waheed

Vaccines 2026, 14(3), 261; https://doi.org/10.3390/vaccines14030261 - 13 Mar 2026

Viewed by 598

Abstract

Background: Cervical carcinoma remains a widespread cancer worldwide, primarily caused by persistent infection with high-risk human papillomavirus (HPV). HPV types 16 and 18 account for approximately 70% of cervical cancer cases. Although prophylactic HPV vaccines are commercially available, their high cost and [...] Read more.

Background: Cervical carcinoma remains a widespread cancer worldwide, primarily caused by persistent infection with high-risk human papillomavirus (HPV). HPV types 16 and 18 account for approximately 70% of cervical cancer cases. Although prophylactic HPV vaccines are commercially available, their high cost and reliance on expensive expression platforms limit their accessibility in developing countries. Objectives: This study aimed to develop a cost-effective, plant-based HPV vaccine candidate by expressing capsomeric HPV-16 and HPV-18 L1 antigens in Brassica oleracea (broccoli). Methods: Modified L1 from HPV types 16 and 18 were designed to retain capsomeric assembly and fused with heat-labile enterotoxin B subunit (LTB). Immunoinformatics analyses were used to assess antigenicity, epitope distribution, and structural characteristics. Codon-optimized genes were cloned using Gateway^® technology and expressed in broccoli via Agrobacterium-mediated transformation. Transgenic plants were validated by PCR and qRT-PCR. Protein accumulation was quantified, and immunogenicity was evaluated in mice. Results: PCR and qRT-PCR confirmed the stable integration of two copies of the LTB-L1 transgenes in broccoli plants. Western blotting detected L1 protein at ~56.5 kDa, indicating the cleavage of the LTB-L1 fusion protein. The correct folding of L1 capsomeres was verified by antigen-capture ELISA. The recombinant proteins accumulated to approximately 0.33% and 0.35% of total soluble protein for HPV-16 and HPV-18, respectively. The immunization of mice with transgenic L1 induced significant humoral immune responses, comparable to those elicited by purified VLPs. Conclusions: The results demonstrate broccoli as a promising platform for the expression of immunogenic HPV L1 capsomeres and highlight its potential for the development of affordable, plant-based HPV vaccines. Full article

(This article belongs to the Special Issue Human Papillomavirus Vaccine Against Cervical Cancer: New Usage Strategies and Coverage Issues)

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20 pages, 2252 KB

Open AccessArticle

Development and Evaluation of Compact Semi-Synthetic Promoters for Enhanced Antigen Expression in Adenoviral-Vectored Vaccines

by Matěj Hlaváč, Susan J. Morris, Barbara Dema, Marta Ulaszewska, Zakia Al-Hareth, Bruno Douradinha and Sarah C. Gilbert

Vaccines 2026, 14(3), 260; https://doi.org/10.3390/vaccines14030260 - 13 Mar 2026

Viewed by 605

Abstract

Background/Objectives: The large size of commonly used regulatory elements such as the cytomegalovirus (CMV) immediate-early promoter imposes a significant burden on the already restricted payload capacity of first-generation adenoviral vectors, potentially hindering the development of multi-antigen vaccine candidates. To address this limitation, we [...] Read more.

Background/Objectives: The large size of commonly used regulatory elements such as the cytomegalovirus (CMV) immediate-early promoter imposes a significant burden on the already restricted payload capacity of first-generation adenoviral vectors, potentially hindering the development of multi-antigen vaccine candidates. To address this limitation, we have engineered a panel of novel, small, semi-synthetic promoters designed to leverage the changes in transcriptomic milieu following adenoviral vector entry. Methods: Eight synthetic enhancer modules (SE1–SE8) were designed in silico, each composed of transcription factor binding sites (TFBSs) previously found in host genes that are upregulated during early adenoviral infection. These synthetic enhancers were coupled with a minimal CMV core promoter to generate a panel of compact semi-synthetic promoters (cSE1–cSE8), and their activity was evaluated in the context of ChAdOx1 viral vectors expressing GFP or a modified Plasmodium falciparum circumsporozoite (CSN) antigen. Promoter performance was characterised in vitro via flow cytometry, RT-qPCR, and Western blotting, and in vivo by quantifying antigen-specific T-cell (IFN-γ ELISpot) and IgG antibody (ELISA) responses in BALB/c mice. Results: In vitro characterisation revealed a wide range of promoter activity across the panel, with cSE3 and cSE5 driving transgene expression levels comparable to the benchmark CMV promoters despite their markedly reduced genomic footprint. In vivo, ChAdOx1 vectors incorporating cSE3 and cSE5 elicited potent antigen-specific T-cell and IgG responses that were comparable to those induced by the larger CMV control promoters. Conclusions: We have successfully developed semi-synthetic promoters that match the potency of the much larger, frequently used CMV promoters whilst simultaneously reducing genomic footprint. These novel regulatory elements will facilitate the design of next-generation vaccines, particularly those requiring large antigens or multi-antigen cassettes. Full article

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

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20 pages, 1189 KB

Open AccessReview

The Feasibility of Developing a Universal SARS-CoV-2 Vaccine

by Mohammed Asaad, Mohamed O. Mustafa, Yaman Al-Haneedi, Lina Shalaby, Rania shams Eldin, Yasar Mohamedahmed, Hadi M. Yassine, Abdallah M. Abdallah and Mohamed M. Emara

Vaccines 2026, 14(3), 259; https://doi.org/10.3390/vaccines14030259 - 13 Mar 2026

Viewed by 818

Abstract

As SARS-CoV-2 continues to evolve with increased transmissibility and immune evasion, the need for vaccines that provide broader and more durable protection has become increasingly urgent. The extensive research spurred by the pandemic has accelerated the development of diverse vaccine platforms, including mRNA, [...] Read more.

As SARS-CoV-2 continues to evolve with increased transmissibility and immune evasion, the need for vaccines that provide broader and more durable protection has become increasingly urgent. The extensive research spurred by the pandemic has accelerated the development of diverse vaccine platforms, including mRNA, DNA, virus-like particles (VLPs), recombinant proteins, and mosaic mono- and polyvalent vaccines. While several of these platforms have reached regulatory approval and widespread clinical employment, others remain under evaluation or in various stages of clinical development. These vaccines have significantly reduced infection rates, severe disease, and hospitalizations, particularly among high-risk group. Nevertheless, the ongoing emergence of novel variants and subvariants has challenged the efficacy of both existing and newly developed vaccines. This evolving landscape underscores the urgent need for a universal SARS-CoV-2 vaccine platform capable of providing comprehensive and long-lasting immunity. In this review, we evaluate current and emerging strategies for SARS-CoV-2 universal vaccine development, with a focus on antigen design, breadth of immune protection, and clinical feasibility. Attention is given to various universal vaccine platforms such as the mosaic polyvalent spike construct, multi-epitope vaccines targeting the receptor-binding domain (RBD), and approaches centered on the conserved S2 subunit of the spike protein. We also discuss strategies leveraging additional conserved viral proteins and T helper (Th) and cytotoxic T lymphocyte (CTL) epitopes from across coronaviruses. By highlighting the advances in these areas, this review provides a framework to guide the rational design of next-generation universal vaccines capable of delivering broad and durable protection against SARS-CoV-2 variants. Full article

(This article belongs to the Collection COVID-19 Vaccine Development and Vaccination)

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16 pages, 876 KB

Open AccessArticle

Monitoring the Performance of National Immunization Programs: Innovative Methodology and Tool for Countries’ Self-Assessment

by Sergio Loayza, Bertha Capistrán, Marcela Contreras, Martha Velandia and Daniel Salas

Vaccines 2026, 14(3), 258; https://doi.org/10.3390/vaccines14030258 - 13 Mar 2026

Viewed by 474

Abstract

Background/Objectives: In the context of its policy of “Reinvigorating Immunization as a Public Good for Universal Health,” the Pan American Health Organization (PAHO) developed a methodology and tool (MD-PAI) to help Member States of the Americas monitor and assess the performance of [...] Read more.

Background/Objectives: In the context of its policy of “Reinvigorating Immunization as a Public Good for Universal Health,” the Pan American Health Organization (PAHO) developed a methodology and tool (MD-PAI) to help Member States of the Americas monitor and assess the performance of their national Expanded Program on Immunization (EPI) for each of the 13 technical components that make up the program. Methods: The MD-PAI was developed in several stages, including review of existing national EPI evaluation methodologies, selection and prioritization of questions for each of the 13 EPI components, piloting of the methodology, final calibration to ensure validity, completeness, reliability, standardization, usefulness, and usability across components and across countries, and publication in the four official languages of the PAHO. Results: The implementation of the MD-PAI enables countries to collect data, document lessons learned, develop action plans to close the most urgent gaps in the short and medium term and enforce the management of the EPI as part of the continuous improvement process. Since its introduction in 2023, fourteen countries in the Americas implemented the MD-PAI, using the results for their short- and medium-term planning and budgeting. Of the 13 components of the EPI, those that have performed best are political priority and planning and programming, while social communication is the component that reported the greatest number of gaps across countries. Conclusions: The PAHO has developed a methodology and tool to help countries to assess their EPIs to identify good practices, gaps and challenges, and develop an action plan to strengthen their programs. However, the impact of vaccination coverages and the epidemiology of vaccine-preventable diseases could take time. Full article

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

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8 pages, 2527 KB

Open AccessConference Report

Conference Report on the 2025 Annual Review of the Essential Programme on Immunization in DR Congo: Dealing with Complexity

by Audry Mulumba, Franck Mboussou, Pablito Nasaka, Augustin Milabyo Byamwitenga, Aimé Cikomola, Cyril Nogier, Thomas Noel Gaha, Mymy Mwika, Benedict Taa Nguimbis, Bridget Farham, Anne Ancia and Benido Impouma

Vaccines 2026, 14(3), 257; https://doi.org/10.3390/vaccines14030257 - 11 Mar 2026

Viewed by 624

Abstract

Background: At the end of each year, stakeholders of the Essential Immunization Programme (EPI) in the DR Congo meet to review progress made and lessons learned from the implementation of the Annual Operational Plan (AOP) and to set priorities for the following year. [...] Read more.

Background: At the end of each year, stakeholders of the Essential Immunization Programme (EPI) in the DR Congo meet to review progress made and lessons learned from the implementation of the Annual Operational Plan (AOP) and to set priorities for the following year. This paper presents a conference report that summarizes the main outcomes of the 2025 annual review meeting, which took place from 15 to 20 December 2025, and attracted 76 participants. Conference takeaways: While the 2024 WUENIC data show that the DR Congo is off-track for the 2030 Immunization agenda targets for all antigens, the administrative coverages were reported as optimal in 2025. EPI activities are planned based on administrative coverages, likely overestimated. In 2025, 47% of health zones in North-Kivu, South-Kivu and Ituri (49 out of 104) were fully or partially controlled by armed groups, leading to partial disruptions of immunization service delivery. In 2025, the DR Congo successfully launched the measles–rubella vaccine introduction preceded by a catch-up vaccination campaign in children aged from 6 months to 14 years old and continued to roll out malaria vaccines using a phased approach. Conclusions: Learning from the implementation of the 2025 AOP, the EPI stakeholders adopted a set of priority actions for the immunization programme in 2026. Full article

(This article belongs to the Special Issue Global Immunization Inequities-Challenges and Solutions)

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Open AccessArticle

Transient Expression and Immunogenicity Assessment of the Dermatophagoides pteronyssinus Der p 2 Allergen Produced in Nicotiana benthamiana

by Kotchaporn Jirananon, Kanokporn Thiganta, Kaewta Rattanapisit, Balamurugan Shanmugaraj and Waranyoo Phoolcharoen

Vaccines 2026, 14(3), 256; https://doi.org/10.3390/vaccines14030256 - 11 Mar 2026

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Abstract

Background: House dust mites (HDM) are one of the significant indoor allergen sources which cause IgE-mediated responses in most of the allergic individuals. HDMs are found in human habitats worldwide and Der p 2 is one of the major clinically relevant HDM allergens [...] Read more.

Background: House dust mites (HDM) are one of the significant indoor allergen sources which cause IgE-mediated responses in most of the allergic individuals. HDMs are found in human habitats worldwide and Der p 2 is one of the major clinically relevant HDM allergens involved in triggering allergic diseases. The recombinant production of Der p 2 in plant systems provides a cost-effective and viable platform for developing diagnostic kits and allergen-specific immunotherapy. Methods: The D. pteronyssinus Der p 2 allergen was transiently expressed in Nicotiana benthamiana and its immunogenicity was evaluated in mice. The Der p 2 coding sequence was cloned into a geminiviral plant expression vector and introduced into N. benthamiana leaves via Agrobacterium tumefaciens-mediated infiltration. Recombinant Der p 2 proteins were purified from the crude extracts and confirmed by sodium dodecyl sulfate–polyacrylamide gel electrophoresis and Western blot. The immunogenicity of the plant-produced Der p 2 proteins was further evaluated by immunizing mice following a prime–boost immunization regimen, and Der p 2-specific antibody responses were assessed by ELISA. Results: Recombinant Der p 2 was successfully expressed and purified from N. benthamiana, and immunized mice developed high levels of Der p 2-specific IgG antibodies, with antibody titers increased after booster immunization. Conclusions: The results demonstrate that the transient expression of Der p 2 in plants is a feasible and effective strategy for producing immunologically active recombinant allergen proteins for diagnostic and potential clinical applications. Full article

(This article belongs to the Special Issue Role of Next Generation Vaccines in Immunotherapeutics)

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Vaccines, Volume 14, Issue 3 (March 2026) – 88 articles

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