Vaccines最新文献

{"title":"mRNA Vaccines Targeting the Conserved SARS-CoV-2 Fusion Machinery Elicit Cross-Variant and Robust Immunity.","authors":"Jun Li, Ke-Meng Li, Shu-Heng Yu, Ming-Hua Li, Xiao-Li Feng, Wei Pang, Yong-Tang Zheng, Jian Zhang","doi":"10.3390/vaccines14090831","DOIUrl":"10.3390/vaccines14090831","url":null,"abstract":"<p><strong>Background/objectives: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":23634,"journal":{"name":"Vaccines","volume":"14 9","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13612069/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149064583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Knowledge of Herpes Zoster and Attitudes Toward Vaccination: A Questionnaire-Based Study in Outpatient and Online Settings.","authors":"Michał Oleszko, Artur Mazur, Lech Zaręba, Nikola Król, Aleksandra Łoś, Hanna Czajka","doi":"10.3390/vaccines14090834","DOIUrl":"10.3390/vaccines14090834","url":null,"abstract":"<p><strong>Background/objectives: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":23634,"journal":{"name":"Vaccines","volume":"14 9","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13612019/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149064615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Rzymski, P. Potential Non-Specific Benefits of Seasonal Influenza Vaccination: Evidence, Knowledge Gaps, and Future Directions. <i>Vaccines</i> 2026, <i>14</i>, 207.","authors":"Piotr Rzymski","doi":"10.3390/vaccines14090833","DOIUrl":"10.3390/vaccines14090833","url":null,"abstract":"<p><p>The author noticed wrong references cited in this published paper [...].</p>","PeriodicalId":23634,"journal":{"name":"Vaccines","volume":"14 9","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13611637/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149064645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Future of Vaccines.","authors":"Ger T Rijkers","doi":"10.3390/vaccines14090832","DOIUrl":"10.3390/vaccines14090832","url":null,"abstract":"<p><p>Humans-as well as all other animals and plant species, for that matter-are surrounded by a world of micro-organisms [...].</p>","PeriodicalId":23634,"journal":{"name":"Vaccines","volume":"14 9","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13611878/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149064833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"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.","authors":"Cristiana Ferrari, Francesco Cama, Lavinia Ponzo, Ilenia Mazzocchi, Claudia Salvi, Lorenzo Ippoliti, Andrea Magrini, Luca Coppeta","doi":"10.3390/vaccines14090835","DOIUrl":"10.3390/vaccines14090835","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>Overall seroprotection in 2025 was 91.8% (931/1014). Stratification showed no significant differences by sex (92.6% female vs. 90.1% male; <i>p</i> = 0.168), age group (92.8% in 18-25 vs. 90.9% in 26-35 years; <i>p</i> = 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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":23634,"journal":{"name":"Vaccines","volume":"14 9","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13611915/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149064613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low Match Between the Emerging 'Mayotte-like' Strain and the 919-Strain Bovine Ephemeral Fever Vaccine.","authors":"Natalia Golender, Dan Gleser, Gabriel Kenigswald, Shani Scheinin, Eyal Klement","doi":"10.3390/vaccines14090830","DOIUrl":"10.3390/vaccines14090830","url":null,"abstract":"<p><p><b>Background/Objectives</b>: 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. <b>Methods</b>: 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. <b>Results</b>: 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 <i>p</i> < 0.01). In unvaccinated 2021-exposed cattle, titers against the 2021 strain were 6.5-fold higher than against ML (<i>p</i> < 0.01). In unvaccinated 2023-exposed cattle, titers against ML were 4.76-fold higher than against the vaccine strain (<i>p</i> < 0.01). Between-strain differences were smaller in vaccinated 2023-exposed cattle. <b>Conclusions:</b> 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.</p>","PeriodicalId":23634,"journal":{"name":"Vaccines","volume":"14 9","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13612049/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149064589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preclinical Evaluation of a Microneedle-Delivered Adjuvanted Microparticulate Gonorrhea Vaccine in Non-Human Primates.","authors":"Amarae Ferguson, Yashkumar Harsoda, Dedeepya Pasupuleti, Tanisha Manoj Arte, Priyal Bagwe, Mahek Gulani, Emmanuel Adediran, Mohammad Uddin, Nikolai Petrovsky, Martin J D'Souza, Susu M Zughaier","doi":"10.3390/vaccines14090827","DOIUrl":"10.3390/vaccines14090827","url":null,"abstract":"<p><p><b>Background/Objectives:</b> 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 <i>Rhesus macaques</i> to provide proof-of-concept data in a relevant large-animal model and to compare different adjuvants. <b>Methods:</b><i>Rhesus macaques</i> 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 <i>N. gonorrhoeae</i>-loaded microparticles to activate dendritic cells was assessed in vitro via changes in surface expression of MHC I, MHC II, CD40, and CD80. <b>Results:</b> The serum from vaccinated primates demonstrated elevated gonococcal-specific IgG and IgA responses compared with naïve controls and measurable bactericidal activity against live, homologous <i>N. gonorrhoeae</i> strains. All adjuvanted formulations increased dendritic cell expression of MHC I, MHC II, CD40, and CD80. <b>Conclusions:</b> 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.</p>","PeriodicalId":23634,"journal":{"name":"Vaccines","volume":"14 9","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13611656/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149064316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New-Onset Pemphigus Following Drug Exposure and Vaccination: A Systematic Review of Reported Cases.","authors":"Gabriele Poddine, Francesco Bellinato, Paolo Gisondi, Giampiero Girolomoni","doi":"10.3390/vaccines14090828","DOIUrl":"10.3390/vaccines14090828","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":23634,"journal":{"name":"Vaccines","volume":"14 9","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13611897/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149064326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunogenicity and Safety of RSVPreF3 OA Coadministration Versus Sequential Administration in Adults: A Systematic Review and Meta-Analysis.","authors":"Shu Jiang, Yan Liu, Ran Cui","doi":"10.3390/vaccines14090826","DOIUrl":"10.3390/vaccines14090826","url":null,"abstract":"<p><strong>Background/objectives: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p><p><strong>Registration: </strong>PROSPERO CRD420261470812.</p>","PeriodicalId":23634,"journal":{"name":"Vaccines","volume":"14 9","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13611371/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149064601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Timing-Dependent Immunostimulatory Activity of Human IFN-β mRNA in Primary Human Myeloid Cells.","authors":"Silvia Fraude-El Ghazi, Maria José Limeres, Rocio Gambaro, Ana Pena Vaquero, Dirk Prawitt, German Islan, Stephan Gehring, Maximiliano L Cacicedo","doi":"10.3390/vaccines14090829","DOIUrl":"10.3390/vaccines14090829","url":null,"abstract":"<p><p><b>Background/Objectives:</b> 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. <b>Methods:</b> 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. <b>Results:</b> 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. <b>Conclusions:</b> 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.</p>","PeriodicalId":23634,"journal":{"name":"Vaccines","volume":"14 9","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13611373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149064797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}