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This review examines the available evidence that repeated annual influenza virus vaccination may have effects on future vaccine responses, and it synthesizes the available data with studies that may indicate potential immunological mechanisms underlying these effects. The goal is to examine the available literature to determine whether these mechanisms can be subverted to improve seasonal influenza virus vaccine efficacy.<\/jats:p>","DOI":"10.1084\/jem.20241283","type":"journal-article","created":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T02:21:09Z","timestamp":1744251669000},"update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":13,"title":["Vaccination against influenza viruses annually: Renewing or narrowing the protective shield?"],"prefix":"10.1084","volume":"222","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0669-1696","authenticated-orcid":true,"given":"Hanover C.","family":"Matz","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01yc7t268","id-type":"ROR","asserted-by":"publisher"}],"name":"Washington University School of Medicine 1 Department of Pathology and Immunology, , St Louis, MO,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6129-2532","authenticated-orcid":true,"given":"Ali H.","family":"Ellebedy","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01yc7t268","id-type":"ROR","asserted-by":"publisher"}],"name":"Washington University School of Medicine 1 Department of Pathology and Immunology, , St Louis, MO,","place":["USA"]},{"id":[{"id":"https:\/\/ror.org\/01yc7t268","id-type":"ROR","asserted-by":"publisher"}],"name":"Center for Vaccines and Immunity to Microbial Pathogens, Washington University School of Medicine 2 , St. Louis, MO,","place":["USA"]},{"id":[{"id":"https:\/\/ror.org\/01yc7t268","id-type":"ROR","asserted-by":"publisher"}],"name":"The Andrew M. and Jane M. 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