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Vaccines
Volume 14
Issue 9
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Vaccines, Volume 14, Issue 9 (September 2026) – 112 articles

Cover Story (view full-size image): Cancer vaccination has four clinical goals: preventing oncogenic infection, intercepting premalignant clones, clearing molecular residual disease, and treating established cancer. In this Review, we propose an antigen-defined, HLA-restricted T-cell vaccine framework organized around seven gates: tumor specificity, natural peptide-HLA presentation, population coverage, persistence under immune selection, selective T-cell recognition, manufacturability, and randomized clinical benefit. It combines a pre-manufactured core of validated shared antigens with a personalized shell when shared targets do not cover the tumor or the patient’s HLA type. Presentation-first selection and rigorous validation provide a practical research agenda for more effective and broadly applicable cancer vaccines. View this paper
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13 pages, 268 KB  
Article
Measles Seroprotection and Catch-Up Vaccination in Medical Students and Other Healthcare Workers at a Large Teaching Hospital: Positive Impact of Mandatory Italian Vaccination Policies
by Cristiana Ferrari, Francesco Cama, Lavinia Ponzo, Ilenia Mazzocchi, Claudia Salvi, Lorenzo Ippoliti, Andrea Magrini and Luca Coppeta
Vaccines 2026, 14(9), 835; https://doi.org/10.3390/vaccines14090835 - 21 Sep 2026
Viewed by 196
Abstract
Background: Measles resurgence across Europe has renewed attention to immunity gaps in healthcare environments. Following decades of sub-optimal coverage, Italy implemented mandatory vaccination under Law 119/2017 to counteract declining rates. However, young adults entering medical training represent a transitional cohort with heterogeneous exposures [...] Read more.
Background: Measles resurgence across Europe has renewed attention to immunity gaps in healthcare environments. Following decades of sub-optimal coverage, Italy implemented mandatory vaccination under Law 119/2017 to counteract declining rates. However, young adults entering medical training represent a transitional cohort with heterogeneous exposures to natural infection versus vaccination. This study evaluated the evolution of measles immunity among medical students and healthcare trainees, assessing the impact of vaccination policies and the operational efficacy of an on-site catch-up vaccination pathway. Methods: We conducted an observational study of 1014 medical-area students and young healthcare workers aged 18–35 years undergoing occupational surveillance in 2025 at Policlinico Tor Vergata, Rome. Measles IgG antibodies were quantified by chemiluminescent immunoassay (VIRCLIA® S/CO > 1.0 defining protection). Findings were compared with baseline institutional data from 2020. Results: Overall seroprotection in 2025 was 91.8% (931/1014). Stratification showed no significant differences by sex (92.6% female vs. 90.1% male; p = 0.168), age group (92.8% in 18–25 vs. 90.9% in 26–35 years; p = 0.249), or nationality. Among the 83 sub-threshold individuals, 42.2% had documented prior immunization, reflecting secondary humoral waning rather than primary vaccine failure. On-site revaccination raised final seroprotection to 95.4%. Comparative assessment demonstrated a significant progressive shift from natural wild-type exposure toward vaccine-induced immunity over the past decade. Conclusions: Mandatory vaccination policies have stabilized baseline protection, yet waning humoral titers among vaccinated young adults present unique operational challenges. A structured occupational protocol combining serological screening, historical verification, and on-site revaccination effectively closes nosocomial immunity gaps. Full article
(This article belongs to the Special Issue Measles Outbreak: Causes and Vaccination Strategies to Overcome)
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17 pages, 1315 KB  
Article
Knowledge of Herpes Zoster and Attitudes Toward Vaccination: A Questionnaire-Based Study in Outpatient and Online Settings
by Michał Oleszko, Artur Mazur, Lech Zaręba, Nikola Król, Aleksandra Łoś and Hanna Czajka
Vaccines 2026, 14(9), 834; https://doi.org/10.3390/vaccines14090834 - 21 Sep 2026
Viewed by 239
Abstract
Background/Objectives: Herpes zoster (HZ) vaccination rates remain low globally despite the availability of effective recombinant vaccines. This study aimed to assess knowledge of HZ and HZ vaccination, willingness to vaccinate, and factors associated with vaccination willingness among at-risk populations in both outpatient clinic [...] Read more.
Background/Objectives: Herpes zoster (HZ) vaccination rates remain low globally despite the availability of effective recombinant vaccines. This study aimed to assess knowledge of HZ and HZ vaccination, willingness to vaccinate, and factors associated with vaccination willingness among at-risk populations in both outpatient clinic and online survey settings in Poland. Methods: A questionnaire-based cross-sectional study was conducted between May and September 2025 in outpatient primary care clinics operated by Medical Center Medyk (Podkarpackie Voivodeship, southeastern Poland) and via online social media platforms. Participants included individuals aged ≥50 years with a history of HZ and individuals aged ≥18 years with at least one recognised HZ risk factor. Multivariable logistic regression and classification and regression tree (CART) analysis were employed to identify predictors of vaccination willingness. Results: Valid responses were obtained from 212 onsite and 241 online participants. A prior history of HZ was significantly associated with correct responses to several knowledge items concerning HZ and HZ vaccination in both settings. Over 40% of initially hesitant or unwilling onsite participants reported a positive change in vaccination intention following medical consultation. CART models demonstrated good discriminative performance (AUC: online 0.841, onsite 0.861). The primary difference between settings was the source of information: online participants relied more heavily on the internet, whereas onsite participants more frequently cited healthcare professionals. Conclusions: Personal experience with HZ and engagement with healthcare professionals significantly influence vaccination willingness. Targeted educational interventions delivered through appropriate communication channels, with emphasis on physician engagement, may help improve vaccination willingness among at-risk populations. Full article
(This article belongs to the Special Issue Acceptance and Hesitancy in Vaccine Uptake: 3rd Edition)
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2 pages, 131 KB  
Correction
Correction: Rzymski, P. Potential Non-Specific Benefits of Seasonal Influenza Vaccination: Evidence, Knowledge Gaps, and Future Directions. Vaccines 2026, 14, 207
by Piotr Rzymski
Vaccines 2026, 14(9), 833; https://doi.org/10.3390/vaccines14090833 - 21 Sep 2026
Viewed by 167
Abstract
The author noticed wrong references cited in this published paper [...] Full article
3 pages, 137 KB  
Editorial
The Future of Vaccines
by Ger T. Rijkers
Vaccines 2026, 14(9), 832; https://doi.org/10.3390/vaccines14090832 - 21 Sep 2026
Viewed by 205
Abstract
Humans—as well as all other animals and plant species, for that matter—are surrounded by a world of micro-organisms [...] Full article
18 pages, 10699 KB  
Article
mRNA Vaccines Targeting the Conserved SARS-CoV-2 Fusion Machinery Elicit Cross-Variant and Robust Immunity
by Jun Li, Ke-Meng Li, Shu-Heng Yu, Ming-Hua Li, Xiao-Li Feng, Wei Pang, Yong-Tang Zheng and Jian Zhang
Vaccines 2026, 14(9), 831; https://doi.org/10.3390/vaccines14090831 - 21 Sep 2026
Viewed by 318
Abstract
Background/Objectives: Despite the gradual waning of global interest in SARS-CoV-2, the continued evolution and emergence of viral variants underscore the need for broadly protective vaccines. Vaccines targeting the highly mutable S1 subunit of the spike protein have shown limited breadth of protection, whereas [...] Read more.
Background/Objectives: Despite the gradual waning of global interest in SARS-CoV-2, the continued evolution and emergence of viral variants underscore the need for broadly protective vaccines. Vaccines targeting the highly mutable S1 subunit of the spike protein have shown limited breadth of protection, whereas conserved regions within the S2 fusion machinery remain critical targets for the development of vaccines effective against future variants. This study evaluated two mRNA-lipid nanoparticle (mRNA-LNP) vaccines encoding HR121, a conserved HR1-HR2-HR1 fusion-intermediate immunogen, in comparison with a recombinant HR121 protein vaccine. Methods: Two mRNA vaccine candidates, TM-HR121 and Fc-HR121, were designed to present HR121 through distinct antigen presentation strategies by incorporating a transmembrane anchor or an IgG Fc domain, respectively. Immunogenicity and protective efficacy were assessed in New Zealand White rabbits, BALB/c mice, and Golden Syrian hamsters. Results: Both mRNA vaccines elicited robust HR121-specific binding antibody responses and broad neutralizing activity against seven SARS-CoV-2 pseudoviruses in rabbits. In mice, the mRNA vaccines induced higher peak IgG titers, a more balanced IgG1/IgG2a profile, stronger antigen-specific IFN-γ responses, and enhanced T-cell responses compared with the recombinant protein vaccine, while maintaining detectable IL-4 responses. In hamsters, immunization with the HR121 mRNA vaccines significantly reduced lung viral RNA levels and attenuated pulmonary pathology and nucleocapsid antigen expression following authentic SARS-CoV-2 challenge. Conclusions: HR121-based mRNA-LNP vaccines successfully elicited cross-variant humoral and cellular immune responses and conferred protective efficacy in small-animal models. These findings support HR121 mRNA-LNP vaccines as a promising strategy for the development of broadly protective coronavirus vaccines targeting conserved S2 fusion epitopes. Full article
(This article belongs to the Special Issue COVID-19 Vaccines in the Post-Pandemic Era: Immune Responses, Boosting Strategies, and Long-Term Outcomes)
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12 pages, 1072 KB  
Article
Low Match Between the Emerging ‘Mayotte-like’ Strain and the 919-Strain Bovine Ephemeral Fever Vaccine
by Natalia Golender, Dan Gleser, Gabriel Kenigswald, Shani Scheinin and Eyal Klement
Vaccines 2026, 14(9), 830; https://doi.org/10.3390/vaccines14090830 - 21 Sep 2026
Viewed by 259
Abstract
Background/Objectives: Bovine ephemeral fever virus (BEFV) causes an economically important arthropod-borne cattle disease. In 2023, a lineage I “Mayotte-like” (ML) strain emerged in Israel during an outbreak in vaccinated herds, raising concerns about its antigenic match with the live-attenuated vaccine based on [...] Read more.
Background/Objectives: Bovine ephemeral fever virus (BEFV) causes an economically important arthropod-borne cattle disease. In 2023, a lineage I “Mayotte-like” (ML) strain emerged in Israel during an outbreak in vaccinated herds, raising concerns about its antigenic match with the live-attenuated vaccine based on Australian strain 919. We compared G-protein neutralizing sites and cross-neutralization among the vaccine strain, Israeli lineage IIIa strains from 2000 and 2021, and ML. Methods: G1–G3 neutralizing-site sequences were compared. Serum-neutralization assays tested all four viruses using sera from 87 cattle across five vaccination/exposure groups. Log2-transformed titers were compared within animals. Results: ML differed from the vaccine strain at eight amino acid positions within G1–G3, whereas the lineage IIIa strains differed from the vaccine strain at three or four positions. In vaccinated, unexposed calves, neutralizing titers against the vaccine and 2021 strains were 4.0- and 2.7-fold higher, respectively, than against ML (both p < 0.01). In unvaccinated 2021-exposed cattle, titers against the 2021 strain were 6.5-fold higher than against ML (p < 0.01). In unvaccinated 2023-exposed cattle, titers against ML were 4.76-fold higher than against the vaccine strain (p < 0.01). Between-strain differences were smaller in vaccinated 2023-exposed cattle. Conclusions: Sequence divergence and cross-neutralization indicate a markedly reduced antigenic match between the Australian 919 vaccine strain and the ML strain. Given the continued circulation and emergence of antigenically divergent BEFV strains and their potential for geographic spread, challenge and field-effectiveness studies are urgently needed to determine the clinical protection afforded by the current vaccine. Lineage-matched or multivalent vaccines should therefore be prioritized to broaden protection against circulating and newly emerging strains. Full article
(This article belongs to the Special Issue Immunization Strategies for Animal Health: 2nd Edition)
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23 pages, 2964 KB  
Article
Timing-Dependent Immunostimulatory Activity of Human IFN-β mRNA in Primary Human Myeloid Cells
by Silvia Fraude-El Ghazi, Maria José Limeres, Rocio Gambaro, Ana Pena Vaquero, Dirk Prawitt, German Islan, Stephan Gehring and Maximiliano L. Cacicedo
Vaccines 2026, 14(9), 829; https://doi.org/10.3390/vaccines14090829 - 20 Sep 2026
Viewed by 310
Abstract
Background/Objectives: Systemic administration of recombinant cytokines for immunomodulation in cancer and chronic infection is limited by toxicity and poor spatial control. Messenger RNA (mRNA)-encoded cytokines offer a programmable alternative, but the immunological consequences of interferon-β (IFN-β) mRNA delivery in primary human immune cells, [...] Read more.
Background/Objectives: Systemic administration of recombinant cytokines for immunomodulation in cancer and chronic infection is limited by toxicity and poor spatial control. Messenger RNA (mRNA)-encoded cytokines offer a programmable alternative, but the immunological consequences of interferon-β (IFN-β) mRNA delivery in primary human immune cells, and its compatibility with co-delivered antigen-encoding mRNA, remain incompletely defined. This study evaluated whether nucleoside-modified, mRNA-encoded human IFN-β can function as a multifunctional immunomodulator with pro-apoptotic activity and timing-dependent immunostimulatory properties. Methods: N1-methylpseudouridine-modified IFN-β mRNA was transfected into HEK293T and HepG2 cell lines and into primary human monocyte-derived dendritic cells (MDDCs) and M2-polarized macrophages (MDMs) using Lipofectamine MessengerMAX, with OVA mRNA as a non-adjuvant control. Apoptosis, interferon-stimulated CXCL10 secretion, activation marker expression, and cytokine profiles were assessed by flow cytometry, ELISA, Western blot, and cytometric bead array. Adjuvant activity was evaluated in MDDCs co-transfected with IFN-β and antigen (EGFP or OVA) mRNA under four temporal delivery regimens. Results: IFN-β mRNA induced time-dependent apoptosis, most pronounced in HepG2 cells, and CXCL10 secretion in both cell lines. In primary immune cells, IFN-β mRNA activated MDDCs, increased pro-inflammatory cytokine secretion, and repolarized M2-like macrophages toward a pro-inflammatory phenotype. In co-transfection experiments, IFN-β mRNA enhanced MDDC activation across regimens, but antigen expression was preserved only when antigen mRNA was delivered before IFN-β mRNA. Conclusions: mRNA-encoded IFN-β combines direct pro-apoptotic activity with programmable, timing-dependent immunostimulatory effects, supporting its development as a component of next-generation mRNA-based immunotherapies and vaccines. Full article
(This article belongs to the Section Vaccine Design, Development, and Delivery)
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13 pages, 637 KB  
Systematic Review
New-Onset Pemphigus Following Drug Exposure and Vaccination: A Systematic Review of Reported Cases
by Gabriele Poddine, Francesco Bellinato, Paolo Gisondi and Giampiero Girolomoni
Vaccines 2026, 14(9), 828; https://doi.org/10.3390/vaccines14090828 - 20 Sep 2026
Viewed by 270
Abstract
Background: Although an increasing number of cases of new-onset pemphigus have been reported following drug exposure or vaccination, the available evidence remains fragmented and distinguishing true trigger-associated disease from coincidental onset continues to represent a major clinical challenge. We performed a systematic review [...] Read more.
Background: Although an increasing number of cases of new-onset pemphigus have been reported following drug exposure or vaccination, the available evidence remains fragmented and distinguishing true trigger-associated disease from coincidental onset continues to represent a major clinical challenge. We performed a systematic review to evaluate the available evidence on drug- and vaccine-associated new-onset pemphigus and to compare their clinical characteristics, management, and outcomes. Methods: This systematic review was conducted according to the PRISMA 2020 statement and prospectively registered in PROSPERO (CRD420261307622). PubMed was searched from database inception to 30 April 2026. Studies reporting individual patients with new-onset pemphigus temporally associated with drug exposure or vaccination were included. Demographic, clinical, immunopathological, therapeutic, and outcome data were extracted and synthesized descriptively because of the anticipated heterogeneity of the available evidence. Results: A total of 20 drug-associated and 26 vaccine-associated cases identified from primary reports were included in the descriptive synthesis. Drug-associated cases demonstrated marked heterogeneity in the implicated agents, broader clinical variability, and a longer median latency, with frequent clinical improvement following withdrawal of the suspected drug when reported. In contrast, vaccine-associated cases occurred predominantly after SARS-CoV-2 vaccination, displayed a substantially shorter latency, and were mainly represented by pemphigus vulgaris and pemphigus foliaceus. Across both groups, systemic corticosteroids constituted the mainstay of treatment, with generally favorable outcomes among patients with available follow-up. However, the available evidence consisted almost exclusively of case reports and small case series, precluding reliable assessment of incidence or causality. Conclusions: Current evidence suggests that drugs and vaccines may act as potential triggers of new-onset pemphigus in susceptible individuals; however, the strength of evidence differs substantially between the two settings. Drug-associated cases generally provide more convincing clinical support for a trigger-related mechanism, whereas vaccine-associated cases require more cautious interpretation because temporal association alone cannot establish causality. Standardized case reporting, prospective pharmacovigilance, and mechanistic studies are needed to strengthen causal inference and improve the recognition and management of trigger-associated pemphigus. Full article
(This article belongs to the Special Issue Immune Responses in Patients with Chronic Disease After Vaccination)
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18 pages, 2511 KB  
Article
Preclinical Evaluation of a Microneedle-Delivered Adjuvanted Microparticulate Gonorrhea Vaccine in Non-Human Primates
by Amarae Ferguson, Yashkumar Harsoda, Dedeepya Pasupuleti, Tanisha Manoj Arte, Priyal Bagwe, Mahek Gulani, Emmanuel Adediran, Mohammad Uddin, Nikolai Petrovsky, Martin J. D’Souza and Susu M. Zughaier
Vaccines 2026, 14(9), 827; https://doi.org/10.3390/vaccines14090827 - 20 Sep 2026
Viewed by 299
Abstract
Background/Objectives: Gonorrhea remains one of the most prevalent sexually transmitted infections globally, with an estimated 82–87 million new infections annually and no licensed vaccine available. Antigenic variability and the lack of durable protective immunity following natural infection have been major obstacles to vaccine [...] Read more.
Background/Objectives: Gonorrhea remains one of the most prevalent sexually transmitted infections globally, with an estimated 82–87 million new infections annually and no licensed vaccine available. Antigenic variability and the lack of durable protective immunity following natural infection have been major obstacles to vaccine development. We previously developed an adjuvanted, formalin-inactivated whole-cell gonococcal microparticle (GC-MP) vaccine delivered by dissolving microneedles and demonstrated that it induced functional antibodies and enhanced bacterial clearance in murine models. Here, we evaluated this GC-MP microneedle platform in Rhesus macaques to provide proof-of-concept data in a relevant large-animal model and to compare different adjuvants. Methods: Rhesus macaques were allocated into five groups and vaccinated, and serum antigen-specific IgG and IgA responses were quantified by ELISA, with functional activity assessed by serum bactericidal assay. In parallel, the potency of delta-inulin-, aluminum-phosphate-, or aluminum-hydroxide-adjuvanted N. gonorrhoeae-loaded microparticles to activate dendritic cells was assessed in vitro via changes in surface expression of MHC I, MHC II, CD40, and CD80. Results: The serum from vaccinated primates demonstrated elevated gonococcal-specific IgG and IgA responses compared with naïve controls and measurable bactericidal activity against live, homologous N. gonorrhoeae strains. All adjuvanted formulations increased dendritic cell expression of MHC I, MHC II, CD40, and CD80. Conclusions: These findings indicate that an adjuvanted whole-cell inactivated gonorrhea vaccine delivered transdermally via microneedles elicits clearly elevated, relative to controls, functional antibody responses, supporting its advancement toward clinical evaluation. Full article
(This article belongs to the Special Issue Biotechnologies Applied in Vaccine Research: 2nd Edition)
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16 pages, 4303 KB  
Systematic Review
Immunogenicity and Safety of RSVPreF3 OA Coadministration Versus Sequential Administration in Adults: A Systematic Review and Meta-Analysis
by Shu Jiang, Yan Liu and Ran Cui
Vaccines 2026, 14(9), 826; https://doi.org/10.3390/vaccines14090826 - 20 Sep 2026
Viewed by 395
Abstract
Background/Objectives: Adults eligible for respiratory syncytial virus (RSV) vaccination may also receive influenza, COVID-19, pneumococcal, or herpes zoster vaccines. We compared immunogenicity and safety between coadministration and sequential schedules. Methods: We searched PubMed, Embase, Web of Science, Scopus, and CENTRAL from inception to [...] Read more.
Background/Objectives: Adults eligible for respiratory syncytial virus (RSV) vaccination may also receive influenza, COVID-19, pneumococcal, or herpes zoster vaccines. We compared immunogenicity and safety between coadministration and sequential schedules. Methods: We searched PubMed, Embase, Web of Science, Scopus, and CENTRAL from inception to 3 August 2026 for randomized trials in adults aged 50 years or older. Eligible trials compared RSVPreF3 OA coadministration with sequential administration of the partner vaccine followed by RSVPreF3 OA. Random-effects models pooled neutralizing-antibody geometric mean ratios (GMRs; coadministration/sequential) separately for RSV-A and RSV-B and risk ratios for safety outcomes. Risk of bias and certainty were assessed using RoB 2 and GRADE, respectively. Results: Six trials randomized 5455 participants. Pooled RSV-A and RSV-B GMRs were 0.895 (95% CI 0.816–0.983) and 0.922 (95% CI 0.837–1.016), respectively. In trial-specific per-protocol analyses, non-inferiority criteria were met for recombinant zoster vaccine (RZV) and 20-valent pneumococcal conjugate vaccine (PCV20) antibody endpoints, but non-inferiority was not demonstrated for SARS-CoV-2 XBB.1.5 neutralizing antibodies (GMR 0.763, 95% CI 0.662–0.885) or the adjuvanted quadrivalent influenza vaccine A/H3N2 response. The pooled risk ratio for serious adverse events was 0.831 (95% CI 0.530–1.303), with limited precision. Certainty was low for RSV-A and very low for RSV-B, mainly reflecting risk of bias and inconsistency. Conclusions: In adults aged 50 years or older, same-day RSVPreF3 OA coadministration was associated with lower RSV-neutralizing antibody responses than sequential administration, while partner-vaccine immunogenicity varied by product and antigen. Non-inferiority was not demonstrated for the SARS-CoV-2 XBB.1.5 and adjuvanted-QIV A/H3N2 antibody endpoints. No clear safety difference between schedules was identified, and the clinical significance of the antibody differences remains uncertain. Registration: PROSPERO CRD420261470812. Full article
(This article belongs to the Section Vaccine Advancement, Efficacy and Safety)
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14 pages, 1260 KB  
Review
Rethinking Candida Vaccine Translation: Barriers, Immunotherapies and a One Health Imperative
by Julie Krier, Francisco A. M. Silva and Célia Fortuna Rodrigues
Vaccines 2026, 14(9), 825; https://doi.org/10.3390/vaccines14090825 - 19 Sep 2026
Viewed by 288
Abstract
Over the past decade, antifungal vaccinology has produced genuine proof of concept: adhesin-based candidates such as NDV-3A have completed Phase II human trials, and reverse-vaccinology pipelines now routinely generate multi-epitope constructs with high predicted population coverage against Candida albicans and the multidrug-resistant Candida [...] Read more.
Over the past decade, antifungal vaccinology has produced genuine proof of concept: adhesin-based candidates such as NDV-3A have completed Phase II human trials, and reverse-vaccinology pipelines now routinely generate multi-epitope constructs with high predicted population coverage against Candida albicans and the multidrug-resistant Candida auris. However, no antifungal vaccine has reached the market, and the reasons for this gap are rarely examined together in a single, critical account. This review argues that the bottleneck is not primarily antigen discovery, but a layered set of translational barriers: biological constraints inherent to a commensal, morphologically plastic pathogen; manufacturing and purity requirements that complicate subunit vaccine production; a historical bias in preclinical animal models toward chemically immunosuppressed, rather than genetically susceptible, hosts; an underutilization of key insights from veterinary medicine; and a fragmented regulatory and commercial landscape that structurally disincentivizes investment in niche, high-risk patient populations. We further examine emerging immunotherapeutic strategies—passive antibody engineering, cytokine-based adjuvant approaches, phytocompound-derived antifungals, and dual-action nanovaccines—as partial, rather than complete, solutions to the immunocompromised-host paradox that limits active immunization in the patients who need protection most. Finally, we situate Candida vaccine development within a One Health and global-equity framework, arguing that diagnostic infrastructure, HLA population diversity, and cold-chain economics must be addressed as part of vaccine design rather than as an afterthought. Full article
(This article belongs to the Special Issue Antibodies in Autoimmune, Chronic, and Infectious Diseases: Pathogenic Mechanisms, Biomarkers, and Vaccine Development)
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24 pages, 4226 KB  
Systematic Review
Efficacy and Response of R21/Matrix-M in Malaria Vaccine: A Systematic Review and Meta-Analysis of Clinical Trials
by Aneeq Ur Rehman, Victory Nnaemeka, Muhammad Hassan Nasir, Nurul Alia Azizan, Ahmed M. Salman and Ahmad Syibli Othman
Vaccines 2026, 14(9), 824; https://doi.org/10.3390/vaccines14090824 - 19 Sep 2026
Viewed by 361
Abstract
Background: R21/Matrix-M is a pre-erythrocytic malaria vaccine supported by a growing body of field-efficacy, immunogenicity, safety, controlled-challenge, and implementation evidence. We synthesized the contemporary human evidence and quantified protection against naturally acquired clinical malaria. Methods: This systematic review and meta-analysis was conducted and [...] Read more.
Background: R21/Matrix-M is a pre-erythrocytic malaria vaccine supported by a growing body of field-efficacy, immunogenicity, safety, controlled-challenge, and implementation evidence. We synthesized the contemporary human evidence and quantified protection against naturally acquired clinical malaria. Methods: This systematic review and meta-analysis was conducted and reported in accordance with PRISMA 2020. PubMed, Scopus, Embase, Web of Science, and Cochrane CENTRAL were searched for studies published from January 2021 to February 2026. The review was not prospectively registered, and no separate protocol was prepared. Eleven studies were retained for the systematic review. The primary quantitative synthesis pooled 12-month Cox proportional-hazards estimates for the first episode of clinical malaria from two independent randomized field trials using generic inverse variance methods. Robustness was examined using a fixed-effect model, a sensitivity analysis that disaggregated the phase III seasonal and standard/perennial transmission strata, and a phase III-only analysis. Booster follow-up and controlled human malaria infection (CHMI) studies were summarized descriptively to avoid double counting and mixing of incompatible endpoints. Results: The primary trial-level meta-analysis yielded a pooled hazard ratio (HR) of 0.265 (95% CI 0.235–0.299), equivalent to vaccine efficacy (VE) of 73.5% (95% CI 70.1–76.5%), with no detected heterogeneity (I2 = 0%; Q = 0.67, p = 0.41; tau2 = 0). Disaggregating the phase III transmission strata produced a similar random-effects estimate (HR 0.270, 95% CI 0.223–0.326; VE 73.0%, 95% CI 67.4–77.7%; I2 = 53.8%). The fixed-effect estimate was HR 0.270 (95% CI 0.240–0.304), and the phase III-only sensitivity analysis remained strongly protective (HR 0.281, 95% CI 0.220–0.357; VE 71.9%). Booster follow-up supported maintained protection, including approximately 80% efficacy during the 12 months after boosting with the 50-microgram Matrix-M regimen. Across the broader evidence base, the vaccine was generally well tolerated and elicited strong anti-CSP/anti-NANP antibody responses. Conclusions: R21/Matrix-M provides substantial protection against naturally acquired clinical malaria, and the central efficacy estimate is robust to alternative analytic specifications. The quantitative evidence base remains small, however, and longer-term effectiveness, severe-malaria protection, booster timing, and post-deployment safety require continued evaluation. Full article
(This article belongs to the Section Vaccines Against Tropical and Other Infectious Diseases)
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17 pages, 1502 KB  
Article
Structured Pharmacist-Led Vaccine Recommendation and Coadministration in Community Pharmacies: Real-World Evidence from Poland
by Ewa Kuczwalska, Anna Maria Dworakowska, Magdalena Skarżyńska and Magdalena Bujalska-Zadrożny
Vaccines 2026, 14(9), 823; https://doi.org/10.3390/vaccines14090823 - 19 Sep 2026
Viewed by 266
Abstract
Background and Objectives: Community pharmacies in Poland administer an expanding range of adult vaccines, including influenza, COVID-19, respiratory syncytial virus (RSV), herpes zoster and pneumococcal vaccines. While pharmacist vaccination services are increasingly available, evidence on structured approaches supporting vaccine coadministration remains limited. This [...] Read more.
Background and Objectives: Community pharmacies in Poland administer an expanding range of adult vaccines, including influenza, COVID-19, respiratory syncytial virus (RSV), herpes zoster and pneumococcal vaccines. While pharmacist vaccination services are increasingly available, evidence on structured approaches supporting vaccine coadministration remains limited. This study assessed whether a structured pharmacist-led recommendation and coadministration protocol was associated with greater uptake of multiple vaccines and same-day coadministration in routine community pharmacy practice. Methods: This non-randomized real-world study used anonymized vaccination records from three community pharmacies in northern Poland between 1 August 2025 and 31 March 2026. One pharmacy implemented a multicomponent protocol combining proactive identification of eligible patients, presumptive recommendation and same-day coadministration, while two comparator pharmacies operated under routine practice. Outcomes included the mean number of vaccine types per patient, the proportion of patients receiving at least two of five analyzed vaccines, same-day coadministration among multi-vaccine patients, and the RSV-to-(influenza + COVID-19) vaccination ratio. A Poisson regression model with robust standard errors was used to assess relative RSV uptake. As the dataset comprised only patients who received at least one vaccination, these findings describe vaccination patterns among presenting, already-vaccinated patients rather than uptake relative to the total eligible or registered pharmacy population, for which denominators were not available. Results: Overall, 3248 patients contributed 5505 unique patient-vaccine events. The intervention pharmacy achieved a higher mean number of vaccine types per patient than comparator pharmacies (2.08 vs. approximately 1.54). The proportion of patients receiving at least two vaccine types was 73.6% (685/931) in the intervention pharmacy compared with 42.7% (990/2317) in comparator pharmacies. Among multi-vaccine patients, same-day coadministration occurred in 92.7% (635/685) of intervention-site patients versus 73.1% (724/990) in comparator pharmacies. Triple-vaccine coadministration visits were observed exclusively in the intervention pharmacy. RSV uptake was higher in the intervention pharmacy (incidence rate ratio 2.17; 95% CI 1.67–2.84; p < 0.001). An age- and sex-adjusted analysis of multi-vaccine uptake yielded a materially unchanged association (adjusted OR 4.42; 95% CI 3.71–5.28) relative to the unadjusted estimate (OR 3.73; 95% CI 3.16–4.41). The exploratory temporal-interaction analysis was not statistically significant when all months were included (interaction IRR 0.84; 95% CI 0.69–1.02; p = 0.085), whereas a sensitivity analysis excluding March 2026 suggested a narrowing relative RSV-rate advantage over time (interaction IRR 0.79; 95% CI 0.70–0.89; p < 0.001). Conclusions: A structured pharmacist-led recommendation and coadministration protocol was associated with substantially greater uptake of multiple vaccines among vaccinated patients, more frequent same-day coadministration and higher RSV uptake compared with routine practice. These findings suggest that workflow organization, proactive patient identification and systematic recommendation strategies may improve the efficiency of adult vaccination delivery in community pharmacies. Larger multicenter studies are warranted to confirm these findings and evaluate individual protocol components. Full article
(This article belongs to the Section Vaccines and Public Health)
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18 pages, 2026 KB  
Article
Does Neoplastic Disease Negatively Affect Serum Antibody Titers Against Core Vaccines in Dogs?
by Paola Dall’Ara, Claudia Pollera, Daniela Invernizzi, Sara Tomassone and Joel Filipe
Vaccines 2026, 14(9), 822; https://doi.org/10.3390/vaccines14090822 - 18 Sep 2026
Viewed by 400
Abstract
Background/Objectives: Neoplasia currently represents the primary cause of death in companion animals worldwide, with one in four dogs developing a tumor during their lifetime. In this scenario, evaluating the immune status against core vaccine-preventable diseases becomes of primary importance to ensure adequate [...] Read more.
Background/Objectives: Neoplasia currently represents the primary cause of death in companion animals worldwide, with one in four dogs developing a tumor during their lifetime. In this scenario, evaluating the immune status against core vaccine-preventable diseases becomes of primary importance to ensure adequate protection in such clinically fragile patients. This study aimed to assess the presence of protective antibody titers (PATs) against core vaccine antigens—canine parvovirus type 2 (CPV-2), canine distemper virus (CDV), and canine adenovirus type 1 (CAdV-1)—in dogs diagnosed with neoplastic disease prior to receiving any antineoplastic therapy. Methods: A total of 120 client-owned, core-vaccinated dogs with various malignant neoplasms were evaluated using an in-clinic semiquantitative assay (VacciCheck®). Results: Overall, high rates of seroprotection were maintained across the study population, with PATs detected in 93.3% of dogs for CPV-2, 86.6% for CAdV-1, and 79.2% for CDV. High protection levels were consistently observed across different sex, age, and body size categories. Solid humoral memory was retained across all tumor types, although dogs with hemolymphopoietic malignancies (especially lymphomas) exhibited slightly lower protection rates (91.9% for CPV-2, 83.8% for CAdV-1, and 75.7% for CDV) compared to other histotypes. Time elapsed since last vaccination influenced CDV and CAdV-1 titers, whereas CPV-2 immunity remained remarkably persistent even beyond 3 years post-vaccination. Conclusions: These findings indicate that high seroprotection against core vaccine antigens is maintained in dogs with neoplastic disease prior to antineoplastic therapy, with no clear evidence of major humoral impairment compared to historical healthy reference data, thereby reassuring veterinary clinicians and pet owners that routine core vaccine boosters may not represent an immediate priority in canine cancer patients. Full article
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17 pages, 4580 KB  
Article
Nucleos(t)ide Analog–Therapeutic Vaccination Switch: A Novel Approach for Safe and Effective Treatment Discontinuation in HBeAg (-) Chronic Hepatitis B Patients
by Sheikh Mohammad Fazle Akbar, Mamun Al Mahtab, Mohammad Abdur Rahim, Sheikh Mohammad Noor-E-Alam, Musarrat Mahtab, Ahmed Lutful Moben, Rokshana Begum, Dulal Chandra Das, Gerardo Guillen, Osamu Yoshida, Ivan Santos Martinez, Yoichi Hiasa, Sakirul Khan and Julio Cesar Aguilar
Vaccines 2026, 14(9), 821; https://doi.org/10.3390/vaccines14090821 - 18 Sep 2026
Viewed by 216
Abstract
Background/Objective: Long-term nucleos(t)ide analog (NUC) therapy effectively suppresses hepatitis B virus (HBV) replication, but it rarely achieves a functional cure and typically requires lifelong administration. A major unmet need in chronic hepatitis B (CHB) is the development of safe and effective strategies to [...] Read more.
Background/Objective: Long-term nucleos(t)ide analog (NUC) therapy effectively suppresses hepatitis B virus (HBV) replication, but it rarely achieves a functional cure and typically requires lifelong administration. A major unmet need in chronic hepatitis B (CHB) is the development of safe and effective strategies to discontinue NUCs without compromising viral control or hepatic safety. This exploratory, randomized pilot study evaluated therapeutic immunization in the context of discontinuation of antiviral therapy in HBeAg-negative CHB. Methods: Twenty-six HBeAg-negative CHB patients receiving long-term therapy with NUCs were randomized to either discontinue NUCs and switch to HeberNasvac (NASVAC), a therapeutic vaccine (n = 13), or receive NASVAC in addition to NUCs (n = 13). Virological, serological, biochemical, and safety parameters were assessed during a 52-week primary follow-up. In particular, ALT and AST were evaluated every 2 weeks during the first 6 months after NUC discontinuation. An extended monitoring period from weeks 96 to 192 was designed to assess virological and biochemical variables. Results: At week 48, HBV DNA remained below 2000 IU/mL in 92.3% of patients who discontinued NUCs and received NASVAC and in 100% of those who received both NUCs and NASVAC. During extended follow-up, HBV DNA < 2000 IU/mL persisted in 84.6% and 76.9% of patients in the NUC discontinuation group at weeks 96 and 192, respectively, and in 100% of patients in the continuation group (NASVAC added to NUCs) at both time points. In the first 48 weeks after NUC discontinuation, NASVAC induced a limited but significant decline in serum quantitative HBsAg. Liver function, renal, and hematological parameters remained stable, without significant ALT abnormalities, biochemical exacerbations, fibrosis progression, or severe adverse events during primary or extended follow-up. None of the patients required restarting treatment. Conclusions: NASVAC-based immunotherapy demonstrated durable virological control, a limited but progressive reduction in qHBsAg, and a strong long-term safety profile following the complete withdrawal of antiviral therapy. This exploratory study suggests that NASVAC can be administered in the context of NUC discontinuation with an acceptable short- and long-term safety profile, but controlled trials are required to determine whether therapeutic vaccination contributes independently to sustained off-treatment viral control. Full article
(This article belongs to the Section Hepatitis Virus Vaccines)
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12 pages, 242 KB  
Article
The Attitude–Uptake Gap in HPV Vaccination Among Adults Aged 18–45 Years in Poland: Sociodemographic and Psychosocial Correlates
by Klaudiusz Mankiewicz, Mikołaj Wachowski, Julia Kłos, Stanisław Klamecki-Cichy and Hanna Krauss
Vaccines 2026, 14(9), 820; https://doi.org/10.3390/vaccines14090820 - 18 Sep 2026
Viewed by 245
Abstract
Background: Favorable attitudes toward human papillomavirus (HPV) vaccination do not necessarily translate into vaccine uptake, particularly among young adults who were too old to benefit from recently expanded adolescent programs. We assessed the gap between attitudes and self-reported HPV vaccination and examined sociodemographic [...] Read more.
Background: Favorable attitudes toward human papillomavirus (HPV) vaccination do not necessarily translate into vaccine uptake, particularly among young adults who were too old to benefit from recently expanded adolescent programs. We assessed the gap between attitudes and self-reported HPV vaccination and examined sociodemographic and psychosocial correlates of uptake in a non-probability sample of young adults residing in Poland. Methods: An anonymous cross-sectional online survey was conducted from 12 January 2025 to 14 August 2026. The analysis included 334 complete responses from adults aged 18–45 years recruited through social media. The 42-item questionnaire assessed sociodemographic characteristics, HPV knowledge, vaccine trust, perceived personal threat, social exposure to vaccinated persons, access, and barriers. Group differences were examined using Pearson chi-square tests. Multivariable logistic regression estimated adjusted odds ratios (aORs) for self-reported vaccination; two respondents reporting sex as other/prefer not to say were excluded from the sex-adjusted model (N=332). Results: Overall, 113/334 participants (33.8%) reported HPV vaccination, whereas 300/334 (89.8%) considered vaccination important. Among unvaccinated respondents, the most frequent barriers were lack of a clinician recommendation (83/221; 37.6%) and cost (75/221; 33.9%). In the adjusted model, vaccination was associated with female sex (aOR 2.49, 95% CI 1.10–5.65), greater vaccine trust (aOR 1.70 per scale point, 95% CI 1.17–2.45), and knowing a vaccinated person (aOR 7.73, 95% CI 4.02–14.86). Compared with participants aged <20 years, those aged 23–25 years (aOR 0.33, 95% CI 0.12–0.86) and >25 years (aOR 0.27, 95% CI 0.09–0.86) had lower odds of vaccination. Objective HPV knowledge, education, urban residence, region, and medical/health-related study or work were not independently associated with uptake in this exploratory model. Model AUC was 0.846. Conclusions: In this non-probability sample, the gap between endorsing HPV vaccination as important and self-reported uptake was substantial; this construct should not be interpreted as an intention–behavior gap. Vaccine confidence and reported social exposure showed stronger cross-sectional associations with HPV vaccination than the exploratory objective-knowledge score, while lack of clinician recommendation and cost remained prominent barriers. These findings support evaluation of catch-up strategies that combine clear clinician recommendation, affordable and convenient access, gender-neutral cancer-prevention communication, and social normalization of vaccination. Full article
(This article belongs to the Special Issue Acceptance and Hesitancy in Vaccine Uptake: 3rd Edition)
29 pages, 1736 KB  
Article
Trust, Access, and the Division of Responsibility for Vaccine Confidence in Central and Eastern Europe: Paired Own-Country and Regional Ratings from a Multi-Stakeholder Professional Panel
by Teodor Cristian Blidaru, Alexandru Rafila, Diana Nastasă, David Sinclair, Petr Smejkal, Yasmin Maor, Ernest Kuchar, Mariano Votta, Luminița Vâlcea and Valeriu Gheorghiță
Vaccines 2026, 14(9), 819; https://doi.org/10.3390/vaccines14090819 - 17 Sep 2026
Viewed by 215
Abstract
Background/Objectives: Immunisation coverage gaps in Central and Eastern Europe (CEE) are commonly attributed to barriers of access. This study measured how the professionals who deliver immunisation services weigh competing barriers, whether their assessments differ when the referent is their own country rather than [...] Read more.
Background/Objectives: Immunisation coverage gaps in Central and Eastern Europe (CEE) are commonly attributed to barriers of access. This study measured how the professionals who deliver immunisation services weigh competing barriers, whether their assessments differ when the referent is their own country rather than the CEE region as a whole, and how they rank candidate interventions on expected impact and near-term feasibility. Methods: Sixty-two professionals working in twelve countries and at the European level (47 based in CEE, 39 of them in Romania) completed a cross-sectional structured survey around a multi-stakeholder meeting in Bucharest (14 May 2026). Respondents rated 15 barriers twice, for their own country and for the CEE region; rated 16 interventions for the expected impact and 12–24-month feasibility; force-ranked their selections; and assigned the lead responsibility for five system functions. Results: Digital misinformation was the highest-rated barrier in every subgroup and at both geographic levels. The assessments differed by geographic referent: within respondents, trust and information barriers were rated more severe for their own country and access barriers more severe for the region (d_z = 0.52), a pattern attenuated but retained after standardising within each level; the same regional object was also described differently by respondents inside and outside CEE (d = 1.02). Across the 16 intervention-level means, the expected impact and feasibility were only weakly and imprecisely associated (r = 0.21, 95% CI −0.32 to 0.64), although, within respondents, the two were modestly correlated (r = 0.33). Continuing professional education for primary care ranked first on expected impact and led the forced-choice ranking in every subgroup. The lead responsibility was the clearest for professional training and least settled for equity monitoring. Conclusions: Barriers were assessed differently depending on whether the referent was the respondent’s own country or the region as a whole. These are professionals’ perceptions, not measured outcomes: access may rank low partly because the panel does not face it personally, and the findings do not place cost and structural determinants second. Regional strategies built on assumptions about neighbouring systems may misallocate attention, and the equity agenda this panel endorses rests on a monitoring function no actor owns. Full article
(This article belongs to the Special Issue Acceptance and Hesitancy in Vaccine Uptake: 3rd Edition)
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14 pages, 8270 KB  
Case Report
Rapid Clinical Improvement Temporally Associated with Off-Label LetiFend® Vaccination in Canine Leishmaniasis: A Case Report
by Tobias Werner, Marius Rămneanţu and Torsten J. Naucke
Vaccines 2026, 14(9), 818; https://doi.org/10.3390/vaccines14090818 - 17 Sep 2026
Viewed by 440
Abstract
Canine leishmaniasis (CanL), caused by Leishmania infantum, can be difficult to manage in dogs with severe clinical disease, particularly when established treatments are impractical or poorly tolerated. We report an approximately 3-year-old mixed-breed dog from Sardinia with clinically manifest CanL, anemia, thrombocytopenia, [...] Read more.
Canine leishmaniasis (CanL), caused by Leishmania infantum, can be difficult to manage in dogs with severe clinical disease, particularly when established treatments are impractical or poorly tolerated. We report an approximately 3-year-old mixed-breed dog from Sardinia with clinically manifest CanL, anemia, thrombocytopenia, marked hyperglobulinemia, and an immunofluorescence antibody test titer of 1:4000. The dog’s condition deteriorated during allopurinol treatment, with profound lethargy, vomiting, diarrhea, and complete refusal of food and water. Because escalation to combination leishmanicidal therapy (meglumine antimoniate or miltefosine) was considered clinically unsuitable in the severely debilitated patient, allopurinol monotherapy was discontinued after 18 days without clinical improvement, and one full commercial dose of the recombinant vaccine LetiFend® was administered subcutaneously off-label. No immediate adverse reaction was observed. Clinical improvement became apparent within approximately 10 days, and near-normal activity returned within three weeks. During follow-up, hematological parameters normalized and serum protein electrophoresis showed an increased albumin/globulin ratio and a reduced gamma-globulin fraction. Domperidone was subsequently introduced as long-term immunomodulatory follow-up, and allopurinol was temporarily reintroduced after transient laboratory deterioration in 2024; the dog remained clinically healthy through July 2026. The close temporal association is clinically noteworthy but cannot establish causality. This hypothesis-generating observation supports controlled investigation of therapeutic vaccination as a potential complementary approach in canine leishmaniasis. Full article
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15 pages, 261 KB  
Article
Factors Associated with Up-to-Date Measles Vaccination Among 2-Year-Old Children in Canada: An Analysis of the 2021 Childhood National Immunization Coverage Survey
by Jeanette Bourne, Anna-Maria Frescura, Samuel Ileka-Priouzeau, Marwa Ebrahim and Julie Laroche
Vaccines 2026, 14(9), 817; https://doi.org/10.3390/vaccines14090817 - 17 Sep 2026
Viewed by 343
Abstract
Background/Objectives: Ongoing measles outbreaks in Canada and worldwide, largely among unvaccinated individuals, emphasize the importance of examining predictors of measles vaccination. This study aims to report on factors associated with up-to-date measles vaccination among 2-year-olds in Canada. Methods: We used national [...] Read more.
Background/Objectives: Ongoing measles outbreaks in Canada and worldwide, largely among unvaccinated individuals, emphasize the importance of examining predictors of measles vaccination. This study aims to report on factors associated with up-to-date measles vaccination among 2-year-olds in Canada. Methods: We used national cross-sectional data from the 2021 childhood National Immunization Coverage Survey (cNICS), which was conducted among 2-year-old Canadian children between 10 January 2022 and 14 July 2022. We examined proportions of vaccinated children by sociodemographic characteristics and conducted multivariable logistic regression analysis to determine factors associated with up-to-date measles vaccination coverage, defined as receiving at least one dose of a measles-containing vaccine by 2 years of age. Results: Among 3118 two-year-olds, 91.6% (95% CI: 89.9–93.1) were up-to-date with their measles vaccines. Lower odds of being up-to-date among 2-year-olds was associated with a household income of less than $60,000 (aOR = 0.35, 95% CI: 0.16–0.75; p < 0.05), experiencing pandemic-related obstacles or delays to vaccination (aOR = 0.23, 95% CI: 0.12–0.43, p < 0.05) and parents being more vaccine-hesitant (aOR = 0.49, 95% CI: 0.26–0.94, p < 0.05). Conclusions: Lower household income, experiencing pandemic-related obstacles, and parental hesitancy contribute to being not up-to-date on measles vaccination among children in Canada. These results support developing targeted programs and communication efforts to help increase measles vaccination coverage in Canada. Full article
(This article belongs to the Special Issue Pediatric Infectious Diseases and Immunization)
33 pages, 11518 KB  
Article
The Silent Vehicle: Validating the Biological Signals and Noises of Baculovirus Vectors in Macrophage-Targeted Vaccines
by Beginda Ridwan, Farrah Putri Salmanida, Rika Wahyuningtyas, Yin-Siew Lai, Mei-Li Wu, Wen-Bin Chung, Chia-Tsai Chang and Ko-Tung Chang
Vaccines 2026, 14(9), 816; https://doi.org/10.3390/vaccines14090816 - 16 Sep 2026
Viewed by 353
Abstract
Objective: The Baculovirus Expression Vector System (BEVS) is an established eukaryotic platform for high-yield recombinant protein production and is widely utilized for generating vaccine antigens, including recombinant classical swine fever virus E2 glycoprotein, African swine fever virus structural proteins (p72, p30, and p54), [...] Read more.
Objective: The Baculovirus Expression Vector System (BEVS) is an established eukaryotic platform for high-yield recombinant protein production and is widely utilized for generating vaccine antigens, including recombinant classical swine fever virus E2 glycoprotein, African swine fever virus structural proteins (p72, p30, and p54), and porcine reproductive and respiratory syndrome virus envelope proteins GP5 and M. These antigens interact with macrophage-associated receptors, including CD163 and CD206, to modulate immune responses through macrophage polarization. However, whether baculovirus vector-derived components intrinsically influence macrophage polarization remains unclear, raising concerns regarding potential impacts on biological activity, vaccine efficacy, and downstream purification strategies. Methods: In this study, an M2-like tumor-associated macrophage (TAM) model capable of repolarizing toward an M1-like phenotype was established to distinguish the transcriptomic effects of the baculovirus vector control (VC) from those of the recombinant antigen (A1). Comparative RNA sequencing, Gene Set Enrichment Analysis (GSEA), functional enrichment analyses, and linear regression analysis were performed to evaluate vector- and antigen-associated transcriptional responses. Results: Comprehensive transcriptomic analysis showed that VC treatment induced only minimal transcriptomic alterations, with limited immune-related pathway enrichment and expression profiles that remained highly similar to those of untreated M2-like TAMs. Furthermore, linear regression analysis demonstrated negligible correlations between VC-induced and A1-induced transcriptional responses indicating that the limited changes associated with the vector backbone did not correspond to the receptor-mediated immune responses elicited by the recombinant antigen. In contrast, A1 stimulation induced distinct transcriptional reprogramming characterized by enrichment of pro-inflammatory and immune-activation pathways and a shift toward an M1-like macrophage phenotype. Conclusions: These findings suggest the negligible correspondence between VC- and A1-induced transcriptional profiles further supports the transcriptomic noises and signals of the baculovirus vector and inserted proteins, reinforcing its suitability as a platform for macrophage-targeted vaccine development while providing a basis for future optimization of downstream purification strategies. Full article
(This article belongs to the Special Issue Challenges to Developing New Vaccines and Improving Existing Platforms)
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11 pages, 227 KB  
Conference Report
Rotavirus Vaccines at 20 Years: Success, Challenges, and the Road Ahead
by Alice S. Carter, Duncan Steele, Mathuram Santosham, Michelle J. Groome and Denise O. Garrett
Vaccines 2026, 14(9), 815; https://doi.org/10.3390/vaccines14090815 - 16 Sep 2026
Viewed by 302
Abstract
Twenty years after the introduction of rotavirus vaccines, the 15th International Rotavirus Symposium convened researchers, clinicians, immunization program managers, and policymakers to review advances in rotavirus epidemiology, immunology, vaccine development, and implementation. Rotavirus vaccination has contributed to sustained reductions in severe rotavirus hospitalizations [...] Read more.
Twenty years after the introduction of rotavirus vaccines, the 15th International Rotavirus Symposium convened researchers, clinicians, immunization program managers, and policymakers to review advances in rotavirus epidemiology, immunology, vaccine development, and implementation. Rotavirus vaccination has contributed to sustained reductions in severe rotavirus hospitalizations and child mortality, yet population-level benefits remain heterogeneous and are constrained by gaps in coverage, supply-related program disruptions, and context-specific vaccine performance. Presenters highlighted evidence from multi-pathogen surveillance confirming that rotavirus remains a leading cause of pediatric diarrhea requiring hospitalization despite widespread vaccine introduction. Accumulating evidence implicates maternally derived antibodies, environmental enteric dysfunction, and early-life microbiome development as contributors to reduced oral vaccine performance in low- and middle-income communities, while recent studies of next-generation vaccine candidates underscore the need for improved correlates of protection and clinically meaningful efficacy endpoints. Collectively, the symposium emphasized that further reductions in rotavirus morbidity and mortality will require strengthening delivery of existing vaccines—including improving coverage, minimizing supply interruptions, and reaching zero-dose and under-immunized children—while sustaining surveillance and investing in integrated enteric disease prevention and next-generation vaccines to optimize protection in high-burden settings. Full article
(This article belongs to the Special Issue The Surveillance and Longterm Impact of Rotavirus Vaccines and Associated Infections in Africa)
12 pages, 785 KB  
Article
A Recombinant RABV-G-Based Chemiluminescence Immunoassay for Quantitative Detection of Rabies Virus Antibodies
by Yan Zhang, Lei Wang, Yanan Han, Na Feng, Ye Feng and Weiyao Sun
Vaccines 2026, 14(9), 814; https://doi.org/10.3390/vaccines14090814 - 16 Sep 2026
Viewed by 277
Abstract
Background: Rabies is a nearly 100% fatal zoonosis, and a rabies virus-neutralizing antibody (RVNA) titre of ≥0.5 IU/mL is the recognized correlate of protection, making post-vaccination serological monitoring essential. However, the gold-standard methods (RFFIT and FAVN) are time-consuming, require live virus, and are [...] Read more.
Background: Rabies is a nearly 100% fatal zoonosis, and a rabies virus-neutralizing antibody (RVNA) titre of ≥0.5 IU/mL is the recognized correlate of protection, making post-vaccination serological monitoring essential. However, the gold-standard methods (RFFIT and FAVN) are time-consuming, require live virus, and are unsuitable for large-scale surveillance, while current ELISA kits often show poor concordance with neutralization tests. Methods: In this study, we established a chemiluminescence immunoassay (CLIA) employing magnetic beads coated with recombinant RABV glycoprotein (short-chain) and an acridinium ester-labeled rabbit anti-dog IgG. Results: The assay exhibited a detection limit of 0.24 IU/mL. Its performance was validated with 250 canine anti-RABV serum samples against the FAVN. The CLIA and FAVN results were strongly correlated (r = 0.9636, p < 0.0001), with a Deming slope of 0.96 (95% confidence interval: 0.92–1.00). The assay achieved a diagnostic sensitivity of 94.4% and a specificity of 97.1%. It demonstrated high accuracy (relative bias within ±10%), good repeatability (intra- and inter-assay coefficients of variation < 8%), and acceptable specificity, showing no cross-reactivity with canine parvovirus, canine distemper virus, or canine parainfluenza virus antibodies. Conclusions: This CLIA kit eliminates the need for live virus, yields quantitative results within 30 min, and offers simple operation and high-throughput capacity, making it a reliable and practical tool for rabies immune monitoring and scientific prevention and control. Full article
(This article belongs to the Section Veterinary Vaccines)
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14 pages, 1995 KB  
Article
Cellular and Humoral Immune Responses in Anti-N Seropositive and Seronegative Vaccinated Participants: Insights from the Bialystok PLUS Study
by Gabriela Trojan, Anna Moniuszko-Malinowska, Justyna Adamczuk, Anna Citko-Rojewska, Maciej Alimowski, Piotr Czupryna, Kiara Sequeira, Hami Nguyen, Justyna Dunaj-Małyszko, Paweł Sowa, Marlena Dubatówka, Magda Łapińska, Sebastian Sołomacha, Małgorzata Kazberuk, Magdalena Chlabicz, Łukasz Kiszkiel, Łukasz Szczerbiński, Piotr Paweł Laskowski and Karol Adam Kamiński
Vaccines 2026, 14(9), 813; https://doi.org/10.3390/vaccines14090813 - 16 Sep 2026
Viewed by 234
Abstract
Background: In the post-pandemic era, SARS-CoV-2 immunity is increasingly shaped by vaccination and previous infection. Understanding the relationship between cellular and humoral immune responses is important for characterizing immunity in vaccinated populations. Methods: This study included 629 participants from the Bialystok PLUS cohort, [...] Read more.
Background: In the post-pandemic era, SARS-CoV-2 immunity is increasingly shaped by vaccination and previous infection. Understanding the relationship between cellular and humoral immune responses is important for characterizing immunity in vaccinated populations. Methods: This study included 629 participants from the Bialystok PLUS cohort, stratified according to anti-N serostatus into anti-N-seronegative (n = 159) and anti-N-seropositive (n = 470) groups. Cellular immune response measurements were available for a subset of 246 participants. Humoral response was assessed using anti-S and anti-N antibodies, while cellular response (OC) was evaluated by interferon-gamma (IFN-γ) release following SARS-CoV-2 antigen stimulation. Group differences were assessed using the Mann–Whitney U test, and associations were evaluated using Spearman’s rank correlations with Benjamini–Hochberg correction. Multivariable linear regression was used to assess the association between anti-N serostatus and cellular response after adjustment for age and sex. Results: Anti-N-seropositive participants had significantly higher cellular responses than anti-N-seronegative participants (median 1752.3 vs. 771.1; p < 0.001). After adjustment for age and sex, anti-N seropositivity remained significantly associated with higher cellular response, corresponding to a 3.57-fold higher geometric mean of OC + 1 (95% CI: 1.90–6.73; p < 0.001). Anti-S antibody levels showed moderate positive correlations with cellular response in both anti-N-seronegative and anti-N-seropositive participants (ρ = 0.45 and ρ = 0.37, respectively), and the association remained significant after adjustment for age, sex, and anti-N serostatus. No significant associations were observed between cellular response and anti-N antibody levels or routine laboratory parameters after correction for multiple comparisons. Conclusions: Anti-N seropositivity was associated with higher SARS-CoV-2-specific cellular immune response among vaccinated participants, and this association remained significant after adjustment for age and sex. The moderate association between anti-S antibody levels and cellular response suggests that humoral and cellular measures provide related but complementary information on SARS-CoV-2-specific immunity. Routine laboratory parameters were not significantly associated with cellular immune response in this cohort. Full article
(This article belongs to the Special Issue COVID-19 Vaccines in the Post-Pandemic Era: Immune Responses, Boosting Strategies, and Long-Term Outcomes)
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32 pages, 1347 KB  
Review
Complementary Roles of RT-PCR and Next-Generation Sequencing in Post-Vaccination SARS-CoV-2 Infection: Clinical Diagnosis, Genomic Characterization, and Surveillance
by Vasiliki E. Georgakopoulou and Vassiliki C. Pitiriga
Vaccines 2026, 14(9), 812; https://doi.org/10.3390/vaccines14090812 - 15 Sep 2026
Viewed by 257
Abstract
SARS-CoV-2 infection after vaccination remains a clinical and public-health challenge because protection against infection may vary with time since vaccination, host factors, previous infection, and ongoing viral evolution. Although vaccination substantially reduces the risk of severe COVID-19, post-vaccination infections may still occur and [...] Read more.
SARS-CoV-2 infection after vaccination remains a clinical and public-health challenge because protection against infection may vary with time since vaccination, host factors, previous infection, and ongoing viral evolution. Although vaccination substantially reduces the risk of severe COVID-19, post-vaccination infections may still occur and may be mild, atypical, or asymptomatic. This narrative review examines the complementary roles of reverse-transcription polymerase chain reaction (RT-PCR) and next-generation sequencing (NGS) in the diagnosis, genomic characterization, and surveillance of post-vaccination SARS-CoV-2 infection. RT-PCR remains the first-line method for confirming acute infection because it is rapid, widely available, and clinically actionable, although its clinical performance depends on appropriate specimen collection and timing. NGS complements RT-PCR by providing viral genomic characterization, including lineage assignment, mutation detection, investigation of suspected transmission clusters, and population-level surveillance. Sequencing may provide additional value in selected settings, particularly suspected reinfection, persistent infection in selected immunocompromised patients, outbreak investigations, and representative or event-triggered genomic surveillance. Its use should therefore be guided by a predefined clinical, epidemiological, or surveillance objective rather than applied routinely to all post-vaccination infections. An integrated strategy combining first-line RT-PCR with objective-driven sequencing can preserve diagnostic efficiency while providing genomic information when it is most likely to influence patient-level investigation, infection-control assessment, or public-health surveillance. Full article
(This article belongs to the Special Issue Next-Generation SARS-CoV-2 Vaccines: Platforms, Evaluation, and Future Directions)
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21 pages, 2435 KB  
Review
Antigen 85B of Mycobacterium tuberculosis: From Immunodominant Antigen to Vaccine Candidate
by Vivek Chauhan, Gaytri Mahajan, Rakesh Kumar, Shrikanth S. Gadad, Subhash C. Chauhan, Chinnaswamy Jagannath and Subramanian Dhandayuthapani
Vaccines 2026, 14(9), 811; https://doi.org/10.3390/vaccines14090811 - 15 Sep 2026
Viewed by 524
Abstract
Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), continues to pose a significant global health challenge despite the existence of effective treatments. The only licensed TB vaccine, Bacillus Calmette–Guérin (BCG), offers inconsistent and generally limited protection against adult pulmonary TB. As a result, the [...] Read more.
Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), continues to pose a significant global health challenge despite the existence of effective treatments. The only licensed TB vaccine, Bacillus Calmette–Guérin (BCG), offers inconsistent and generally limited protection against adult pulmonary TB. As a result, the pursuit of more effective TB vaccines has intensified over the past two decades, prompting the evaluation of several immunodominant Mtb antigens as vaccines. Among these, antigen 85B (Ag85B) has emerged as a promising candidate due to its critical roles in mycobacterial cell wall biosynthesis, host cell adhesion, and the induction of immune responses. Ag85B has been incorporated into diverse vaccine platforms, including subunit, recombinant, DNA, and mRNA-based vaccines. Evidence from preclinical and clinical studies indicates that Ag85B-containing vaccine formulations elicit robust cellular immune responses, and in many instances, enhance protection against TB. Collectively, these findings position Ag85B as a central component in the development of next-generation TB vaccines. This review examines the biological properties and immunological significance of Ag85B and provides an overview of recent advances in Ag85B-based vaccine strategies. Full article
(This article belongs to the Special Issue Vaccines for Tuberculosis Control)
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9 pages, 227 KB  
Article
Influenza Vaccination Status and Clinical Outcomes Among Adults Hospitalized with Community-Acquired Pneumonia: A Retrospective Cohort from Saudi Arabia
by Shouq M. Alzaaqi, Ayman Banjar, Majed A. Almoghrabi, Seham F. Basheer, Sami Alsaedi, Saeed M. Algarni, Ezzuddin A. Okmi, Sarah A. Barzanji, Samah A. Bukhari, Abeer S. Alasmari, Abdullah M. Alyemeny, Abdulaziz A. Alshaalan and Haytham A. Sheerah
Vaccines 2026, 14(9), 810; https://doi.org/10.3390/vaccines14090810 - 14 Sep 2026
Viewed by 250
Abstract
Background: Influenza vaccination is widely recommended to prevent influenza and its complications; however, its association with clinical outcomes among high-risk populations remains uncertain. This study aimed to investigate the association between influenza vaccination status and clinical outcomes among adults hospitalized with community-acquired pneumonia [...] Read more.
Background: Influenza vaccination is widely recommended to prevent influenza and its complications; however, its association with clinical outcomes among high-risk populations remains uncertain. This study aimed to investigate the association between influenza vaccination status and clinical outcomes among adults hospitalized with community-acquired pneumonia (CAP) in Saudi Arabia. Methods: This retrospective cohort study included adults hospitalized with CAP in Saudi public hospitals between October 2023 and March 2024. Data on demographic characteristics, comorbidities, influenza vaccination status, laboratory-confirmed influenza infection, intensive care unit (ICU) admission, in-hospital mortality, and length of hospital stay were obtained from electronic health records. Logistic regression analyses were performed to evaluate the associations between influenza vaccination and clinical outcomes. Results: Among 485 patients, 114 (23.5%) had received the seasonal influenza vaccine. The prevalence of laboratory-confirmed influenza infection was similar among vaccinated and unvaccinated patients (57.9% vs. 58.5%, p-value = 0.910). Vaccinated patients were less likely to require ICU admission (1.8% vs. 7.5%, p-value = 0.025), while no significant differences were observed in length of hospital stay or in-hospital mortality. After adjustment for age, sex, and comorbidities, influenza vaccination was associated with lower odds of ICU admission (OR = 0.200, 95% CI: 0.045, 0.894). No significant associations were observed between influenza vaccination and laboratory-confirmed influenza infection, length of hospital stay, or in-hospital mortality. Conclusions: Among adults hospitalized with CAP in Saudi Arabia, influenza vaccination was associated with a lower likelihood of ICU admission, supporting its potential role in reducing disease severity among high-risk populations. Full article
(This article belongs to the Special Issue The Effectiveness of Influenza Vaccine)
3 pages, 163 KB  
Editorial
Towards Better Vaccines: Enhancing Benefits, Mitigating Risks
by Kay Choong See
Vaccines 2026, 14(9), 809; https://doi.org/10.3390/vaccines14090809 - 14 Sep 2026
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Abstract
For any medical intervention, benefits must outweigh risks [...] Full article
(This article belongs to the Special Issue Clinical Strategies to Improve Efficacy, Effectiveness, and Safety of Vaccination in Humans)
14 pages, 899 KB  
Article
Immunogenicity and Safety of a Single Booster Dose of Sabin-Strain Inactivated Poliovirus Vaccine in Adolescents and Adults: A Phase IV, Open-Label Trial
by Xiaoshu Zhang, Weixiao Han, Jianfeng Wang, Yu Tang, Yanan Ji, Liping Lu, Junxia Zuo, Yijing Nie, Yajing Yao, Jun Li, Dan Yu and Jing An
Vaccines 2026, 14(9), 808; https://doi.org/10.3390/vaccines14090808 - 14 Sep 2026
Viewed by 279
Abstract
Background: In China, the current national immunisation schedule extends only to 4 years of age, and no polio booster dose is recommended for adolescents or adults, with data on immunogenicity and safety in these populations lacking. This phase IV trial evaluated the immunogenicity [...] Read more.
Background: In China, the current national immunisation schedule extends only to 4 years of age, and no polio booster dose is recommended for adolescents or adults, with data on immunogenicity and safety in these populations lacking. This phase IV trial evaluated the immunogenicity and safety of a single booster dose of Sabin-strain inactivated poliovirus vaccine (sIPV) in Chinese adolescents and adults. Methods: This phase IV, open-label trial enrolled 120 healthy participants, comprising 60 adolescents aged 7–17 years and 60 adults aged 18–50 years, who received a single booster dose of sIPV. Participants were enrolled and vaccinated in Gansu Province, China, between 21 October and 1 November 2025. Immunogenicity was assessed by neutralising antibody titres against poliovirus types 1, 2, and 3 before and 30 days post-vaccination. Safety was evaluated through monitoring of adverse events throughout the 30-day follow-up period. Results: Following a single sIPV booster dose, seropositivity rates reached 100% for all three poliovirus serotypes in both age groups. Post-vaccination geometric mean titres (GMTs) for types 1, 2, and 3 were 1748.29, 3961.77, and 2089.08 in adolescents, and 1902.58, 4434.39, and 2256.16 in adults, respectively, with no significant between-group differences. Seroconversion rates for type 3 were significantly higher in adults than in adolescents (98.33% vs. 86.67%, p = 0.032). Geometric mean increases (GMIs) were significantly higher in adults for type 1 (72.12 vs. 28.10, p = 0.008) and type 3 (316.14 vs. 45.56, p < 0.001). The vaccine was well tolerated; vaccine-related adverse events were reported in 17.50% of participants, all mild to moderate, with no vaccine-related serious adverse events. Conclusions: A single booster dose of sIPV induced robust neutralising antibody responses across all three poliovirus serotypes in both adolescents and adults, with a favourable safety profile. Adults with lower baseline immunity derived proportionally greater fold-increases in antibody titres. Full article
(This article belongs to the Section Vaccine Advancement, Efficacy and Safety)
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13 pages, 964 KB  
Article
Preparing for Future Group B Streptococcus Vaccines: Perspectives of Pregnant Women in Australia
by Prabha H. Andraweera, Emma Jeffs, Bing Wang and Helen S. Marshall
Vaccines 2026, 14(9), 807; https://doi.org/10.3390/vaccines14090807 - 14 Sep 2026
Viewed by 242
Abstract
Background: Vaccines for Group B Streptococcus (GBS) intended for pregnant women are currently in advanced stages of clinical trials. Conducting preparatory research now can help identify factors influencing GBS vaccine acceptance and potential challenges to future implementation. Methods: This qualitative study recruited participants [...] Read more.
Background: Vaccines for Group B Streptococcus (GBS) intended for pregnant women are currently in advanced stages of clinical trials. Conducting preparatory research now can help identify factors influencing GBS vaccine acceptance and potential challenges to future implementation. Methods: This qualitative study recruited participants nationally through social media and antenatal clinics of a maternity hospital in South Australia between December 2024 and August 2025. Eligible participants were pregnant women aged ≥18 years residing in Australia. Online interviews and focus group discussions (FGDs) were held to explore pregnant women’s knowledge and perceptions of GBS, experiences with current screening and management strategies, and views on future maternal GBS vaccination. Twenty-five women participated in FGDs and six in individual interviews; FGD group sizes ranged from two to five participants. Data were analysed using inductive content analysis. Results: A total of 31 pregnant women participated, aged 19–43 years. Most participants (51.6%) were from South Australia, 87.1% had tertiary education, and 51.6% were employed in the health sector. Five themes were identified: (1) infant wellbeing is the dominant driver of vaccine acceptance, (2) maternal vaccination is preferred over current antibiotic prophylaxis, (3) perceived uncertainty about vaccine safety and knowledge gaps fuel caution, (4) accessible and flexible vaccination delivery models are desired, and (5) multimodal, woman-centred communication delivered through trusted healthcare providers is required. Conclusions: Findings highlight the importance of addressing knowledge and safety concerns and incorporating accessible, flexible and woman-centred approaches into the planning of future maternal GBS vaccination programmes. Full article
(This article belongs to the Special Issue Maternal and Infant Vaccines)
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10 pages, 457 KB  
Article
Analysis of Clinical Characteristics of Pertussis in Children Aged 0–6 Years in Tertiary and Pediatric Hospitals of Jiangsu Province from January to May 2024
by Yan Xu, Mei Li, Qiang Chen, Chengmei Jia, Lingyan Tang, Yuanbao Liu, Zhiguo Wang and Xiang Huo
Vaccines 2026, 14(9), 806; https://doi.org/10.3390/vaccines14090806 - 14 Sep 2026
Viewed by 369
Abstract
Objective: To analyze the clinical manifestations and hospitalization-related factors among children with pertussis, and to provide scientific support for pertussis prevention, control, clinical diagnosis, and treatment. Methods: From January through May 2024, children aged 0–6 years with a confirmed diagnosis of pertussis at [...] Read more.
Objective: To analyze the clinical manifestations and hospitalization-related factors among children with pertussis, and to provide scientific support for pertussis prevention, control, clinical diagnosis, and treatment. Methods: From January through May 2024, children aged 0–6 years with a confirmed diagnosis of pertussis at tertiary hospitals and children’s hospitals in Jiangsu Province were enrolled in this investigation. Descriptive statistical analysis was performed to explore the clinical characteristics of the children, with stratification by age, immunization status, time from onset to diagnosis, and visit type. Logistic regression analysis was applied to identify factors associated with hospitalization. Results: In total, 3361 children were recruited, with the 6-year age group accounting for the highest proportion (35.4%). Severe symptoms such as apnea and cyanosis were more common in infants aged 0–5 months. Children who received four doses of the pertussis vaccine had significantly lower rates of paroxysmal cough, vomiting, cyanosis and apnea than unvaccinated children (p < 0.001). Delayed diagnosis (≥15 days after onset) was found in 26.89% of children, who had a higher prevalence of vomiting and cyanosis. The prevalence of all clinical symptoms was higher in hospitalized children than in outpatients. Age 0–2 months, delayed diagnosis, cyanosis, paroxysmal cough, and fever were positively associated with hospitalization, whereas receipt of ≥1 dose was negatively associated with hospitalization. Conclusions: Infants ≤2 months are at high risk for severe pertussis and hospitalization. Early diagnosis, timely vaccination, and close monitoring of children presenting with cyanosis, paroxysmal cough, and fever are critical to reducing pertussis-related hospitalization risk, especially in infants. Full article
(This article belongs to the Special Issue Diphtheria-Tetanus-Pertussis (DTP) Vaccination Strategy)
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