{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:12:57Z","timestamp":1787008377343,"version":"build-2736575974"},"reference-count":160,"publisher":"Oxford University Press (OUP)","issue":"12","funder":[{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Despite all we have learned since 1918 about influenza virus and immunity, available influenza vaccines remain inadequate to control outbreaks of unexpected strains. Universal vaccines not requiring strain matching would be a major improvement. Their composition would be independent of predicting circulating viruses and thus potentially effective against unexpected drift or pandemic strains. This commentary explores progress with candidate universal vaccines based on various target antigens. Candidates include vaccines based on conserved viral proteins such as nucleoprotein and matrix, on the conserved hemagglutinin (HA) stem, and various combinations. Discussion covers the differing evidence for each candidate vaccine demonstrating protection in animals against influenza viruses of widely divergent HA subtypes and groups; durability of protection; routes of administration, including mucosal, providing local immunity; and reduction of transmission. Human trials of some candidate universal vaccines have been completed or are underway. Interestingly, the HA stem, like nucleoprotein and matrix, induces immunity that permits some virus replication and emergence of escape mutants fit enough to cause disease. Vaccination with multiple target antigens will thus have advantages over use of single antigens. Ultimately, a universal vaccine providing long-term protection against all influenza virus strains might contribute to pandemic control and routine vaccination.<\/jats:p>","DOI":"10.1093\/aje\/kwy145","type":"journal-article","created":{"date-parts":[[2018,7,31]],"date-time":"2018-07-31T23:17:02Z","timestamp":1533079022000},"page":"2603-2614","source":"Crossref","is-referenced-by-count":33,"title":["Universal Influenza Vaccines: Progress in Achieving Broad Cross-Protection In Vivo"],"prefix":"10.1093","volume":"187","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6311-6890","authenticated-orcid":false,"given":"Suzanne L","family":"Epstein","sequence":"first","affiliation":[{"name":"Division of Cellular and Gene Therapies, Office of Tissues and Advanced Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,8,1]]},"reference":[{"key":"2019120223305637500_kwy145C1","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1128\/JB.89.1.170-174.1965","article-title":"Induction of partial specific heterotypic immunity in mice by a single infection with influenza A virus","volume":"89","author":"Schulman","year":"1965","journal-title":"J Bacteriol"},{"issue":"2","key":"2019120223305637500_kwy145C2","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1128\/iai.29.2.654-662.1980","article-title":"Outcome of influenza infection: effect of site of initial infection and heterotypic immunity","volume":"29","author":"Yetter","year":"1980","journal-title":"Infect Immun"},{"issue":"2","key":"2019120223305637500_kwy145C3","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1128\/iai.29.2.650-653.1980","article-title":"Heterotypic immunity to influenza in ferrets","volume":"29","author":"Yetter","year":"1980","journal-title":"Infect Immun"},{"issue":"2","key":"2019120223305637500_kwy145C4","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1084\/jem.159.2.365","article-title":"Most influenza A virus-specific memory cytotoxic T lymphocytes react with antigenic epitopes associated with internal virus determinants","volume":"159","author":"Kees","year":"1984","journal-title":"J Exp Med"},{"issue":"2","key":"2019120223305637500_kwy145C5","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1084\/jem.160.2.552","article-title":"The influenza-A virus nucleoprotein gene controls the induction of both subtype specific and cross-reactive cytotoxic T-cells","volume":"160","author":"Townsend","year":"1984","journal-title":"J Exp Med"},{"issue":"2","key":"2019120223305637500_kwy145C6","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1084\/jem.165.2.408","article-title":"Identification of viral molecules recognized by influenza-specific human cytotoxic lymphocytes-T","volume":"165","author":"Gotch","year":"1987","journal-title":"J Exp Med"},{"issue":"11","key":"2019120223305637500_kwy145C7","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1586\/erv.10.123","article-title":"Cross-protective immunity to influenza A viruses","volume":"9","author":"Epstein","year":"2010","journal-title":"Expert Rev Vaccines"},{"key":"2019120223305637500_kwy145C8","first-page":"285","article-title":"Universal immunity to influenza must outwit immune evasion","volume":"5","author":"Qui\u00f1ones-Parra","year":"2014","journal-title":"Front Microbiol"},{"issue":"1","key":"2019120223305637500_kwy145C9","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1128\/JVI.68.1.517-520.1994","article-title":"Protection against the mouse-adapted A\/FM\/1\/47 strain of influenza A virus in mice by a monoclonal antibody with cross-neutralizing activity among H1 and H2 strains","volume":"68","author":"Okuno","year":"1994","journal-title":"J Virol"},{"issue":"1","key":"2019120223305637500_kwy145C10","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1038\/icb.1950.5","article-title":"Studies in experimental immunology of influenza. 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