Vaccine最新文献

{"title":"Clinical immunization safety assessment (CISA) project: COVID-19 vaccine consultations and case reviews","authors":"Paula M. Campbell ,&nbsp;Gabriella J. Ess ,&nbsp;Allison Lale ,&nbsp;Kawsar R. Talaat ,&nbsp;Elizabeth D. Barnett ,&nbsp;Stephen I. Pelton ,&nbsp;Elizabeth P. Schlaudecker ,&nbsp;Mary Staat ,&nbsp;Melissa S. Stockwell ,&nbsp;Phillip S. LaRussa ,&nbsp;Emmanuel B. Walter ,&nbsp;Michael J. Smith ,&nbsp;Neal A. Halsey ,&nbsp;Nicola P. Klein ,&nbsp;Michael M. McNeil ,&nbsp;Karen R. Broder ,&nbsp;Tom T. Shimabukuro ,&nbsp;Matthew B. Crist ,&nbsp;Tarayn A. Fairlie ,&nbsp;Shashi Sharma ,&nbsp;Kathryn M. Edwards","doi":"10.1016/j.vaccine.2025.127781","DOIUrl":"10.1016/j.vaccine.2025.127781","url":null,"abstract":"<div><h3>Background</h3><div>The Clinical Immunization Safety Assessment (CISA) Project is a network of vaccine safety experts from the Centers for Disease Control and Prevention (CDC) Immunization Safety Office (ISO) and seven medical research centers. CISA responds to inquiries from U.S. healthcare providers (HCPs) and conducts vaccine safety research. This report summarizes the CISA approach to addressing provider vaccine safety inquiries during the COVID-19 pandemic and describes these consultations.</div></div><div><h3>Methods</h3><div>During the COVID-19 pandemic, CDC established a 24/7 on-call CISA consultation service. Inquiries were reviewed, and some of the most clinically complex were selected for comprehensive, structured CISA clinical case consultations. After confidential consultations, provider satisfaction surveys were sent, and providers were queried about patient outcomes and whether patients tolerated subsequent COVID-19 vaccinations.</div></div><div><h3>Results</h3><div>From December 14, 2020, through December 31, 2022, CDC staff and CISA investigators conducted 79 comprehensive clinical case consultations (73 regarding adverse events following immunization (AEFI) after COVID-19 vaccine, and 6 pre-vaccination questions). Of the 73 AEFI consultations, 31 (42 %) included neurologic and 14 (19 %) allergic or hypersensitivity symptoms. Cardiology and hematology inquiries comprised most of the remainder. Twenty-four (30 %) provider satisfaction surveys were returned; all respondents found the service helpful. Of 38 (79 total; 48 %) returned patient follow-up surveys, 14 (37 %) reported that subsequent COVID-19 vaccines were administered and were well-tolerated in case patients.</div></div><div><h3>Discussion</h3><div>Despite low participation rate in satisfaction and patient follow-up surveys, the CISA consultation service provided timely COVID-19 vaccine safety evaluations for HCPs through comprehensive clinical case consultations and vaccine safety guidance, a unique role in the pandemic response.</div></div>","PeriodicalId":23491,"journal":{"name":"Vaccine","volume":"65 ","pages":"Article 127781"},"PeriodicalIF":4.5,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145188123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"T cell-mediated clearance of porcine reproductive and respiratory syndrome virus (PRRSV) from the lung characterized by machine learning analysis in vaccinated and unvaccinated pigs","authors":"Andrew Noel ,&nbsp;Jianqiang Zhang ,&nbsp;Teerawut Nedumpun ,&nbsp;Panchan Sitthicharoenchai ,&nbsp;Baoqing Guo ,&nbsp;Reid Phillips ,&nbsp;Marius Kunze ,&nbsp;Oliver Gomez-Duran ,&nbsp;Jennifer Groeltz-Thrush ,&nbsp;Emily Rahe ,&nbsp;Michael C. Rahe","doi":"10.1016/j.vaccine.2025.127793","DOIUrl":"10.1016/j.vaccine.2025.127793","url":null,"abstract":"<div><div>Porcine reproductive and respiratory syndrome (PRRS) modified live virus (MLV) vaccines likely confer partial protection against heterologous wild type challenge through broadly reactive T cells. Therefore, the efficacy of Ingelvac PRRS® MLV alone and reconstituted with Ingelvac CircoFLEX® was assessed by comparing the ability to induce a robust cell-mediated immune response and confer protection against challenge. This study utilized both classic immune assays and machine learning software for measuring the cell-mediated immune response to PRRSV vaccination and challenge. Both vaccine groups had significantly reduced viremia, lung viral load, gross and microscopic lung lesions and improved average daily gain compared to the mock vaccinated group. The T cell analysis in the lung revealed a robust response to PRRSV infection leading to marked clearance of virus from the lung in the absence of neutralizing antibodies.</div></div>","PeriodicalId":23491,"journal":{"name":"Vaccine","volume":"65 ","pages":"Article 127793"},"PeriodicalIF":4.5,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145160260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunogenicity of the abbreviated one-week intradermal rabies pre-exposure prophylaxis and its boostability in health-care workers: A retrospective observational cohort study","authors":"M.A. Ashwini,&nbsp;Shipra Gupta,&nbsp;Lonika Lodha,&nbsp;Arya Ramachandran ,&nbsp;Amrita Pattanaik ,&nbsp;V.S. Sujatha,&nbsp;Reeta S. Mani","doi":"10.1016/j.vaccine.2025.127787","DOIUrl":"10.1016/j.vaccine.2025.127787","url":null,"abstract":"<div><div>Rabies pre-exposure prophylaxis (PrEP) is recommended for those at high occupational risk, including health care workers (HCWs) in rabies-endemic settings. Following institutional biosafety protocols, HCWs receive a one-week, two-site intradermal (ID) PrEP regimen. This retrospective vaccination records review assessed the immunogenicity of this regimen following primary vaccination and evaluated the immune response to a booster dose administered 1–3 years later. 92 HCWs with mean baseline rabies virus neutralizing antibody (RVNA) titres of 0.13 IU/mL showed adequate seroconversion (RVNA ≥ 0.5 IU/mL) by day 14, with mean titre of 13.40 IU/mL. 39 HCWs with mean pre-booster titre of 2.76 IU/mL received a booster 1–3 years later and mean post-booster titres were 51.13 IU/mL, indicating a strong anamnestic response. The regimen elicited robust seroconversion in all HCWs and induced a strong secondary immune response, supporting the immunogenicity and long-term boostability of this shortened regimen in high-risk occupational settings.</div></div>","PeriodicalId":23491,"journal":{"name":"Vaccine","volume":"65 ","pages":"Article 127787"},"PeriodicalIF":4.5,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145188167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Time intervals from vaccine administration to reimbursement for an updated Advisory Committee on Immunization Practices (ACIP) recommendation: Evidence from pneumococcal conjugate vaccinations among privately insured adults, 2021–2022","authors":"Hannah G. Rosenblum ,&nbsp;Charles M. Carpenter ,&nbsp;Tina Trosclair ,&nbsp;RajReni Kaul ,&nbsp;Bo-Hyun Cho ,&nbsp;Miwako Kobayashi ,&nbsp;Andrew J. Leidner","doi":"10.1016/j.vaccine.2025.127665","DOIUrl":"10.1016/j.vaccine.2025.127665","url":null,"abstract":"<div><h3>Background</h3><div>Vaccination implementation challenges can lead to lower uptake, reducing health and economic benefits from vaccines. Healthcare provider confidence in receiving timely reimbursement for vaccination is one such potential challenge for newly recommended vaccines. This study investigates the time interval between pneumococcal vaccination and reimbursement.</div></div><div><h3>Methods</h3><div>We used 2021–2022 Merative™ MarketScan® Commercial Database and Medicare Database (MarketScan) data among those aged 19–64 and ≥65 years for two vaccines: the 13-valent pneumococcal conjugate vaccine (PCV13), recommended in 2012; and the newer 20-valent PCV (PCV20), recommended in 2021. We characterized vaccination claims, patient demographics, and time intervals between vaccination and reimbursement.</div></div><div><h3>Results</h3><div>During the study period, MarketScan® contained 24,508 PCV13 and 53,194 PCV20 outpatient vaccination claims for individuals aged 19–64 years and 14,693 PCV13 and 18,277 PCV20 claims for those aged ≥65 years. Among those aged 19–64 years, mean reimbursement interval of outpatient claims was 25.3 (PCV13) and 26.8 (PCV20) days. Among those aged ≥65 years, mean interval was longer, particularly for PCV20, with 31.5 (PCV13) and 41.3 days (PCV20). Outpatient claims reimbursement intervals were longer in non-metropolitan compared to metropolitan areas. Pharmacy claims had shorter intervals than outpatient claims, across both vaccines and age groups. PCV13 intervals were similar throughout the observation period, while PCV20 intervals were longer immediately following the updated ACIP recommendation and declined over time. Approximately 10 % of outpatient claims had intervals greater than 30 days among those aged 19–64 years and greater than 60 days for those aged ≥65 years.</div></div><div><h3>Conclusion</h3><div>During the 5 months following the ACIP recommendation, claims for the newer vaccine (PCV20) took longer to reimburse, but the interval stabilized after about 6 months to a length comparable to PCV13. Claims from outpatient settings and non-metropolitan areas took longer to reimburse, with some claims still experiencing longer intervals several months post-recommendation.</div></div>","PeriodicalId":23491,"journal":{"name":"Vaccine","volume":"64 ","pages":"Article 127665"},"PeriodicalIF":4.5,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145158214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond the post: The impact of politized anti-vaccine misinformation comments and challenges of correction on social media","authors":"Xiaohui Cao ,&nbsp;Porismita Borah ,&nbsp;Danielle Ka Lai Lee ,&nbsp;Anastasia Vishnevskaya ,&nbsp;Yan Su ,&nbsp;Kyle Lorenzano","doi":"10.1016/j.vaccine.2025.127760","DOIUrl":"10.1016/j.vaccine.2025.127760","url":null,"abstract":"<div><div>Despite the proven effectiveness of HPV vaccines in preventing cervical cancer, vaccination rates in the United States remain low, in part because parents' decisions are heavily shaped by misinformation encountered on social media. Using an online experimental design (<em>N</em> = 1039), this study investigated the effects of politized anti-vaccine misinformation comments under CDC posts on parents' vaccination hesitancy as well as the emotional mechanism of this impact. Individual's need for cognition (NFC) was also examined as a moderator. Furthermore, we explored whether CDC corrections help to mitigate these negative effects. Results showed a moderated mediation relationship. Participants exposed to politized anti-vaccine misinformation comments reported higher HPV vaccine hesitancy, with negative emotions toward the original post mediating this association. However, this pattern was observed only among participants with low to medium levels of NFC. For individuals with high NFC, the relationship between negative emotions and vaccine hesitancy, as well as the mediation effect of negative emotions, were not significant. Corrections from the CDC did not help decrease the negative emotions and HPV vaccine hesitancy. This study extends prior research by investigating the effectiveness of second-layer correction comments, an increasingly common but underexamined form of misinformation correction strategy in the current interactive social media environments.</div></div>","PeriodicalId":23491,"journal":{"name":"Vaccine","volume":"65 ","pages":"Article 127760"},"PeriodicalIF":4.5,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145160261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating cost-effectiveness of RSV vaccination strategies for older adults in the Netherlands","authors":"Florian Zeevat ,&nbsp;Jos Luttjeboer ,&nbsp;Koos Korsten ,&nbsp;Michiel van Boven ,&nbsp;Maarten J. Postma ,&nbsp;Simon van der Pol ,&nbsp;Cornelis Boersma","doi":"10.1016/j.vaccine.2025.127735","DOIUrl":"10.1016/j.vaccine.2025.127735","url":null,"abstract":"<div><h3>Objective</h3><div>This study evaluates the cost-effectiveness of respiratory syncytial virus (RSV) vaccination for older adults in the Netherlands, aiming to identify the most effective vaccination strategy.</div></div><div><h3>Methods</h3><div>A static decision tree cost-effectiveness model was developed to compare no vaccination with various RSV vaccination strategies for Dutch adults over six RSV seasons. Strategies included vaccinating adults aged ≥60, ≥75, and ≥75 combined with high-risk individuals aged 60–74. Each was assessed with two- and three-year intervals. The model incorporated health outcomes and costs associated with RSV disease and vaccination from a societal perspective, with a lifetime horizon. Recent incidence data were used, and vaccine effectiveness was based on efficacy from a meta-analysis for outpatient settings and real-world effectiveness data for inpatient settings. A probabilistic sensitivity analysis was conducted, using a €50,000 per quality-adjusted life year (QALY) willingness-to-pay threshold.</div></div><div><h3>Results</h3><div>Vaccinating individuals aged ≥75 years and high-risk groups every three years could prevent approximately 19,000 general practitioner visits, 3300 hospitalizations (including 245 intensive care admissions), and 870 deaths in the first year. This strategy would avoid €29.5 million in healthcare costs and €6.3 million in productivity losses, gaining 2900 QALYs. It was cost-effective, with an average cost-effectiveness ratio (ACER) of €30,804/QALY. The most cost-effective strategy was vaccinating ≥75 year-olds every three years, with an incremental cost-effectiveness ratio (ICER) of 23,080/QALY compared to no vaccination. Vaccinating all ≥60-year-olds every three years resulted in the highest QALY gain, with an ACER of €39,918/QALY. Compared to the ≥75 and high-risk strategy, this approach had an ICER of €107,623/QALY, whereas the 75+ and high-risk strategy had an ICER of €61,987/QALY compared to the ≥75 strategy alone. Biennial strategies were associated with higher ACERs and were dominated in incremental comparisons.</div></div><div><h3>Conclusion</h3><div>RSV vaccination for older adults in the Netherlands can be cost-effective, particularly when vaccinating every three years.</div></div>","PeriodicalId":23491,"journal":{"name":"Vaccine","volume":"65 ","pages":"Article 127735"},"PeriodicalIF":4.5,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145160262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rationalizing recommendations for influenza and COVID-19 vaccines","authors":"Jessica A. Breznik ,&nbsp;Matthew S. Miller ,&nbsp;Dawn M.E. Bowdish","doi":"10.1016/j.vaccine.2025.127775","DOIUrl":"10.1016/j.vaccine.2025.127775","url":null,"abstract":"<div><div>Influenza vaccination saves lives, reduces short-term and long-term health consequences, decreases healthcare utilization, and improves pregnancy outcomes and infant health. Consequently, many, although not all, high-income countries have influenza vaccination policies that recognize both the direct (prevention of infection) and indirect (e.g., reduction in transmission and absenteeism, exacerbations of other health conditions) benefits of vaccination. Vaccination policies for COVID-19 are less consistent, even though COVID-19 continues to cause more infections than influenza. Indeed, some countries recommend COVID-19 vaccination only for older adults and individuals who are severely immunocompromised. Herein we compare influenza and COVID-19 vaccination effectiveness against both acute infection and indirect effects of infection. We find that COVID-19 vaccines are equivalent to, or outperform, influenza vaccines when comparing protection from symptomatic infection, reduction in severe disease, safety profiles, and real-world effectiveness. We propose that expansion of COVID-19 vaccination policies would reduce disruptions to school, work, and healthcare systems, in addition to preventing hospitalizations and severe disease.</div></div>","PeriodicalId":23491,"journal":{"name":"Vaccine","volume":"65 ","pages":"Article 127775"},"PeriodicalIF":4.5,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145128265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Health economics and vaccine financing in the eastern Mediterranean region: A needs assessment","authors":"Palwasha Anwari ,&nbsp;Gerald Sume ,&nbsp;Wedyan Meshreky ,&nbsp;Nathalie Vande Maele ,&nbsp;So Yoon Sim ,&nbsp;Karene Hoi Ting Yeung ,&nbsp;Diana Kizza ,&nbsp;Philipp Lambach ,&nbsp;Maarten Paul Maria Jansen ,&nbsp;Raymond Hutubessy ,&nbsp;Quamrul Hasan","doi":"10.1016/j.vaccine.2025.127780","DOIUrl":"10.1016/j.vaccine.2025.127780","url":null,"abstract":"<div><h3>Introduction</h3><div>The World Health Organization Eastern Mediterranean Region (EMR) faces a high burden of vaccine-preventable diseases requiring efficient use of limited resources. A regional needs assessment was conducted to evaluate the current application of health economics and vaccine financing in national immunization programmes and policy formulation, identify capacity gaps, and inform tailored technical support.</div></div><div><h3>Methods</h3><div>A structured online survey was administered between January 28 and February 18, 2025. It targeted expended programme on immunization (EPI) managers and National Immunization Technical Advisory Group (NITAG) chairs across all 22 EMR countries. The questionnaire explored five thematic areas: current capacity in health economics and vaccine financing, training and capacity-building needs, demand for technical support, data availability and use in decision-making, and strategic planning for vaccine financing among immunization stakeholders at Ministry of Health and in NITAGs. The survey used multiple-choice, Likert-scale, and open-ended questions. Results were analyzed using descriptive statistics and disaggregated by income level.</div></div><div><h3>Results</h3><div>The response rate was 73 % (16/22 countries). Only three countries (19 %) reported full integration of health economics within their immunization programmes, while 56 % (<em>n</em> = 9) reported minimal or no integration. Three countries had a dedicated health economics focal person for immunization. In two high-income countries immunization programmes demonstrated stronger capacity in health economics, whereas the rest of countries demonstrated low to moderate levels. Ten countries (63 %) rated their capacity in financial forecasting and planning for immunization as moderate or high, but eleven (69 %) rated their capacity in cost-effectiveness analysis and vaccine financial sustainability as low to none. Access to data varied, with 25 % of countries finding it easily accessible.</div></div><div><h3>Conclusion</h3><div>The findings highlight the need to strengthen the integration of health economics and vaccine financing into immunization programmes and policy decision-making across the EMR, irrespective of income level. Tailored capacity-building, technical support, and cross-sectoral collaboration, particularly with academia, are essential.</div></div>","PeriodicalId":23491,"journal":{"name":"Vaccine","volume":"65 ","pages":"Article 127780"},"PeriodicalIF":4.5,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145160263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A mosaic H3 subtype live attenuated influenza vaccine elicits broad immune responses to influenza a viruses","authors":"Zhuolin Yang ,&nbsp;Shumiao Zhang ,&nbsp;Yifan Zhao ,&nbsp;Ximeng Ma ,&nbsp;Xue Han ,&nbsp;Yuxuan Lei ,&nbsp;Huanle Luo ,&nbsp;Qian Xie ,&nbsp;Xuejie Liu ,&nbsp;Yuelong Shu","doi":"10.1016/j.vaccine.2025.127776","DOIUrl":"10.1016/j.vaccine.2025.127776","url":null,"abstract":"<div><div>Influenza A(H3N2) viruses are typically associated with reduced vaccine effectiveness (VE), especially in the elderly. To address this challenge, we developed a novel live attenuated influenza vaccine (LAIV) expressing a mosaic H3 hemagglutinin designed to maximize potential cytotoxic T lymphocyte (CTL) epitope coverage, using the A/Leningrad/134/17/57 (H2N2) backbone. The resulting mosaic reassortant virus exhibited temperature-sensitive and cold-adapted phenotypes and caused no significant weight loss or clinical signs in mice. Following prime-boost intranasal immunization in BALB/c mice, robust cellular immune responses were observed, with increased frequencies of splenic and pulmonary IFN-γ⁺ and IL-4⁺ T cells after restimulation, as well as elevated levels of pulmonary tissue-resident memory T cells. High levels of cross-reactive IgA were also detected in nasal and bronchoalveolar lavage fluids, covering multiple influenza virus strains. Additionally, broad serum antibody responses were induced, with HI and MN antibodies targeting 8 and 7 of 9 H3N2 vaccine strains. Virus challenge results showed that the mosaic reassortant virus conferred complete protection against the homologous-subtype strain A/Aichi/2/1968 (H3N2) and partial protection against the heterosubtypic strains A/Puerto Rico/8/1934 (H1N1) and A/Hunan/42443/2015 (H1N1), with survival rates of 20 % and 40 %, respectively. In contrast, all mice vaccinated with traditional monovalent LAIV or inactivated influenza vaccine showed 0 % survival. Moreover, lung viral loads showed a decreasing trend after infection, and pathological damage in the lungs was markedly alleviated compared to other groups. These findings suggest that combining the mosaic antigen with LAIV induces multi-layered immune responses and provides a rational vaccine design strategy for addressing the rapid antigenic evolution of H3N2 viruses.</div></div>","PeriodicalId":23491,"journal":{"name":"Vaccine","volume":"65 ","pages":"Article 127776"},"PeriodicalIF":4.5,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145128298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nontoxic, multi-domain botulinum neurotoxin-LCHCN as vaccines against botulism.","authors":"A. Przedpelski ,&nbsp;W.H. Tepp ,&nbsp;S. Gupta ,&nbsp;J.T. Barbieri ,&nbsp;S. Pellett","doi":"10.1016/j.vaccine.2025.127779","DOIUrl":"10.1016/j.vaccine.2025.127779","url":null,"abstract":"<div><div>Botulinum neurotoxins (BoNTs), the causative agents of botulism, are proteins consisting of an N-terminal catalytic Light Chain (LC) and a C-terminal Heavy Chain (HC), which comprises a LC-translocation domain (HC_N) and a receptor binding domain (HC_C). There are seven BoNT serotypes (A-G) and multiple subtypes. Currently, there is no approved vaccine against botulism available for human use. Several studies have investigated BoNT domains, multi-domains, or mutated holotoxins as candidate BoNT vaccines. However, residual toxicity has been observed in mutated full-length BoNTs and multi-domain (LCHC_N) vaccines. In this study, six-individual point substitutions (6M) were introduced into the substrate binding and cleavage sites, zinc binding motif, and LC translocation region of LCHC_N/A1 and LCHC_N/B1, which possessed no detectable toxicity in mice at 200 μg, being &gt;40-million-fold less toxic than full-length BoNT. IP immunization of mice with 6MLCHC_N/A1 or 6MLCHC_N/B1 elicited a strong IgG response that protected against high dose challenge with BoNT/A1 or BoNT/B1, respectively. 4MBoNT/B1 and 7MBoNT/B1 were also engineered and found to elicit strong IgG responses that protected against high dose challenge with BoNT/B1. Thus, multi-domain inactivation may yield potent and safe vaccines against other BoNT-serotypes and BoNT-like proteins. The strategy of systematic inactivation of multiple functional domains by targeted single amino acid substitutions to decrease toxicity, combined with investigations of the most immunogenic and protective domains, provides a robust platform for protein toxin vaccines for humans and animals.</div></div>","PeriodicalId":23491,"journal":{"name":"Vaccine","volume":"65 ","pages":"Article 127779"},"PeriodicalIF":4.5,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145128266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}