{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T06:32:08Z","timestamp":1788503528893,"version":"build-2803163510"},"reference-count":187,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,1,21]],"date-time":"2021-01-21T00:00:00Z","timestamp":1611187200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100015691","name":"Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI139473"],"award-info":[{"award-number":["AI139473"]}],"id":[{"id":"10.13039\/100015691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Influenza poses a huge threat to global public health. Influenza vaccines are the most effective and cost-effective means to control influenza. Current influenza vaccines mainly induce neutralizing antibodies against highly variable globular head of hemagglutinin and lack cross-protection. Vaccine adjuvants have been approved to enhance seasonal influenza vaccine efficacy in the elderly and spare influenza vaccine doses. Clinical studies found that MF59 and AS03-adjuvanted influenza vaccines could induce cross-protective immunity against non-vaccine viral strains. In addition to MF59 and AS03 adjuvants, experimental adjuvants, such as Toll-like receptor agonists, saponin-based adjuvants, cholera toxin and heat-labile enterotoxin-based mucosal adjuvants, and physical adjuvants, are also able to broaden influenza vaccine-induced immune responses against non-vaccine strains. This review focuses on introducing the various types of adjuvants capable of assisting current influenza vaccines to induce cross-protective immunity in preclinical and clinical studies. Mechanisms of licensed MF59 and AS03 adjuvants to induce cross-protective immunity are also introduced. Vaccine adjuvants hold a great promise to adjuvant influenza vaccines to induce cross-protective immunity.<\/jats:p>","DOI":"10.3390\/vaccines9020075","type":"journal-article","created":{"date-parts":[[2021,1,21]],"date-time":"2021-01-21T11:49:40Z","timestamp":1611229780000},"page":"75","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Adjuvantation of Influenza Vaccines to Induce Cross-Protective Immunity"],"prefix":"10.3390","volume":"9","author":[{"given":"Zhuofan","family":"Li","sequence":"first","affiliation":[{"name":"Biomedical &amp; Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, 7 Greenhouse Road, Avedisian Hall, Room 480, Kingston, RI 02881, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiwen","family":"Zhao","sequence":"additional","affiliation":[{"name":"Biomedical &amp; Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, 7 Greenhouse Road, Avedisian Hall, Room 480, Kingston, RI 02881, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9640-4493","authenticated-orcid":false,"given":"Yibo","family":"Li","sequence":"additional","affiliation":[{"name":"Biomedical &amp; Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, 7 Greenhouse Road, Avedisian Hall, Room 480, Kingston, RI 02881, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyuan","family":"Chen","sequence":"additional","affiliation":[{"name":"Biomedical &amp; Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, 7 Greenhouse Road, Avedisian Hall, Room 480, Kingston, RI 02881, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,21]]},"reference":[{"key":"ref_1","first-page":"659","article-title":"Influenza update: A review of currently available vaccines","volume":"36","author":"Clayville","year":"2011","journal-title":"P & T"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"D49","DOI":"10.1016\/j.vaccine.2008.07.039","article-title":"The biology of influenza viruses","volume":"26","author":"Bouvier","year":"2008","journal-title":"Vaccine"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1038\/nrmicro.2017.118","article-title":"The evolution of seasonal influenza viruses","volume":"16","author":"Petrova","year":"2018","journal-title":"Nat. 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