{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T20:18:40Z","timestamp":1793823520317,"version":"4.6.1"},"reference-count":164,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T00:00:00Z","timestamp":1776643200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007311","name":"Cleveland Clinic","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007311","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Seasonal influenza vaccination remains the most effective strategy for reducing influenza burden and preventing severe disease. Despite decades of vaccine development, the seasonal influenza vaccine is administered intramuscularly and provides suboptimal and highly variable effectiveness depending on host factors, pre-existing immunity, and antigenic match between vaccine and circulating strains. Recent advances in vaccine development have highlighted the potential of intranasal vaccine delivery as a strategy to increase protection against influenza virus infection by inducing local and systemic immune responses. Across multiple intranasal platforms under development, mucosal immunity, particularly secretory IgA and T- and B-cell immune responses, plays a central role in shaping protection against influenza virus infection. Live-attenuated influenza vaccines (LAIV) elicit protective immune responses, particularly in the pediatric population, and remain the only currently licensed intranasal seasonal influenza vaccine. However, variable performance in adults, strain-dependent viral fitness, and clinical contraindications have limited their broader applicability. These limitations have driven the development of next-generation intranasal influenza vaccine platforms designed to preserve the immunological advantages of mucosal vaccination while improving consistency, safety, and applicability across diverse populations. This review synthesizes current knowledge on licensed and emerging intranasal influenza vaccine platforms, including replicating viral platforms and non-replicating platforms, and discusses key immunological mechanisms, challenges, and translational progress. Together, these advances underscore the growing potential of intranasal vaccination as a next-generation strategy to improve influenza control.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1809302","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T05:25:11Z","timestamp":1776662711000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Next-generation intranasal influenza vaccines: mechanisms, platforms, and translational progress"],"prefix":"10.3389","volume":"17","author":[{"given":"Laise Rodrigues","family":"Reis","sequence":"first","affiliation":[{"name":"Florida Research and Innovation Center, Cleveland Clinic","place":["Port Saint Lucie, FL, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ted M.","family":"Ross","sequence":"additional","affiliation":[{"name":"Florida Research and Innovation Center, Cleveland Clinic","place":["Port Saint Lucie, FL, United States"]},{"name":"Department of Infection Biology, Lerner Research Institute, Cleveland Clinic","place":["Cleveland, OH, United States"]},{"name":"Department of Infectious Diseases, University of Georgia","place":["Athens, GA, United States"]},{"name":"Center for Vaccines and Immunology, University of Georgia","place":["Athens, GA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines12111251","article-title":"Systematic review on influenza burden in emerging markets in 2018-2023-an evidence update to guide influenza vaccination recommendations","volume":"12","author":"Kyaw","year":"2024","journal-title":"Vaccines (Basel)"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1007\/s12325-023-02610-1","article-title":"Understanding the global burden of influenza in adults aged 18-64 years: a systematic literature review 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