{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T13:18:02Z","timestamp":1787318282043,"version":"build-2736575974"},"reference-count":25,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2016,10,28]],"date-time":"2016-10-28T00:00:00Z","timestamp":1477612800000},"content-version":"vor","delay-in-days":1031,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Background. \u2003The national stockpile for influenza pandemic preparedness includes vaccines against an array of strains and adjuvants that could be utilized to induce immunologic priming as a pandemic wave emerges. We assessed the feasibility of a strategy that allows the flexibility of postmanufacture mixture of vaccine and adjuvant at the point of care.<\/jats:p>\n                  <jats:p>Methods. \u2003We conducted a randomized, double-blind, multicenter trial among healthy adults aged 18\u201349 years who received 2 doses of inactivated influenza A\/Indonesia\/05\/2005 (H5N1 clade 2.2.3) virus vaccine containing either 3.75, 7.5, or 15 \u00b5g of hemagglutinin (HA) with or without AS03 adjuvant, administered 21 days apart. Subjects were observed for local (injection site) and systemic reactogenicity and adverse events. Sera were tested for hemagglutination inhibition (HAI) and microneutralization (MN) antibody levels against the homologous strain and 4 heterologous avian strains.<\/jats:p>\n                  <jats:p>Results. \u2003Vaccine containing ASO3 adjuvant was associated with significantly more local reactions compared with nonadjuvanted vaccine, but these were short-lived and resolved spontaneously. Although the immune response to nonadjuvanted vaccine was poor, 2 doses of AS03-adjuvanted vaccine containing as little as 3.75 \u00b5g of HA elicited robust immune responses resulting in seroprotective titers (\u22651:40) to the homologous strain in \u226586% of subjects by HAI and in 95% of subjects by MN. Cross-clade antibody responses were also observed with AS03-adjuvanted vaccine, but not nonadjuvanted vaccine.<\/jats:p>\n                  <jats:p>Conclusions. \u2003AS03 adjuvant formulated with inactivated vaccine at the administration site significantly enhanced the immune responses to H5N1 vaccine and has the potential to markedly improve vaccine responses and accelerate delivery during an influenza pandemic.<\/jats:p>\n                  <jats:p>Clinical Trials Registration. \u2003NCT01317758.<\/jats:p>","DOI":"10.1093\/ofid\/ofu091","type":"journal-article","created":{"date-parts":[[2014,9,10]],"date-time":"2014-09-10T20:31:31Z","timestamp":1410381091000},"source":"Crossref","is-referenced-by-count":32,"title":["Safety, Reactogenicity, and Immunogenicity of Inactivated Monovalent Influenza A(H5N1) Virus Vaccine Administered With or Without AS03 Adjuvant"],"prefix":"10.1093","volume":"1","author":[{"given":"Wilbur H.","family":"Chen","sequence":"first","affiliation":[{"name":"Center for Vaccine Development, University of Maryland School of Medicine, Baltimore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa A.","family":"Jackson","sequence":"additional","affiliation":[{"name":"Group Health Research Institute, Seattle, Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn M.","family":"Edwards","sequence":"additional","affiliation":[{"name":"Vanderbilt Vaccine Research Program, Vanderbilt University School of Medicine, Nashville, Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy A.","family":"Keitel","sequence":"additional","affiliation":[{"name":"Baylor College of Medicine, Houston, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather","family":"Hill","sequence":"additional","affiliation":[{"name":"EMMES Corporation, Rockville, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana L.","family":"Noah","sequence":"additional","affiliation":[{"name":"Southern Research, Birmingham, Alabama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. Buddy","family":"Creech","sequence":"additional","affiliation":[{"name":"Vanderbilt Vaccine Research Program, Vanderbilt University School of Medicine, Nashville, Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shital M.","family":"Patel","sequence":"additional","affiliation":[{"name":"Baylor College of Medicine, Houston, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Mangal","sequence":"additional","affiliation":[{"name":"EMMES Corporation, Rockville, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen L.","family":"Kotloff","sequence":"additional","affiliation":[{"name":"Center for Vaccine Development, University of Maryland School of Medicine, Baltimore"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,10,8]]},"reference":[{"key":"2020081009571917800_OFU091C1","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1016\/S1473-3099(08)70232-9","article-title":"Stockpiling prepandemic influenza vaccines: a new cornerstone of pandemic preparedness plans","volume":"8","author":"Jennings","year":"2008","journal-title":"Lancet Infect Dis"},{"key":"2020081009571917800_OFU091C2","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1093\/infdis\/jiq093","article-title":"Safety and immunogenicity of influenza A H5 subunit vaccines: effect of vaccine schedule and antigenic variant","volume":"203","author":"Belshe","year":"2011","journal-title":"J Infect Dis"},{"key":"2020081009571917800_OFU091C3","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1056\/NEJMoa055778","article-title":"Safety and immunogenicity of an inactivated subvirion influenza A (H5N1) vaccine","volume":"354","author":"Treanor","year":"2006","journal-title":"N Engl J Med"},{"key":"2020081009571917800_OFU091C4","doi-asserted-by":"crossref","first-page":"1732","DOI":"10.1016\/S0264-410X(00)00395-9","article-title":"Safety and immunogenicity of a recombinant hemagglutinin vaccine for H5 influenza in humans","volume":"19","author":"Treanor","year":"2001","journal-title":"Vaccine"},{"key":"2020081009571917800_OFU091C5","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1128\/CVI.00368-08","article-title":"Qualification of the hemagglutination inhibition assay in support of pandemic influenza vaccine licensure","volume":"16","author":"Noah","year":"2009","journal-title":"Clin Vaccine Immunol"},{"key":"2020081009571917800_OFU091C6","doi-asserted-by":"crossref","first-page":"4240","DOI":"10.1016\/j.vaccine.2012.04.044","article-title":"Phase 2 assessment of the safety and immunogenicity of two inactivated pandemic monovalent H1N1 vaccines in adults as a component of the U.S. pandemic preparedness plan in 2009","volume":"30","author":"Chen","year":"2012","journal-title":"Vaccine"},{"key":"2020081009571917800_OFU091C7","first-page":"323","article-title":"Adjuvants for pandemic influenza vaccines","volume":"333","author":"Atmar","year":"2009","journal-title":"Curr Top Microbiol Immunol"},{"key":"2020081009571917800_OFU091C8","doi-asserted-by":"crossref","first-page":"1657","DOI":"10.1016\/S0140-6736(06)68656-X","article-title":"Safety and immunogenicity of an inactivated split-virion influenza A\/Vietnam\/1194\/2004 (H5N1) vaccine: phase I randomised trial","volume":"367","author":"Bresson","year":"2006","journal-title":"Lancet"},{"key":"2020081009571917800_OFU091C9","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1086\/592172","article-title":"Safety and immunogenicity of an inactivated influenza A\/H5N1 vaccine given with or without aluminum hydroxide to healthy adults: results of a phase I-II randomized clinical trial","volume":"198","author":"Keitel","year":"2008","journal-title":"J Infect Dis"},{"key":"2020081009571917800_OFU091C10","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1016\/S0140-6736(07)61297-5","article-title":"Antigen sparing and cross-reactive immunity with an adjuvanted rH5N1 prototype pandemic influenza vaccine: a randomised controlled trial","volume":"370","author":"Leroux-Roels","year":"2007","journal-title":"Lancet"},{"key":"2020081009571917800_OFU091C11","doi-asserted-by":"crossref","first-page":"1644","DOI":"10.1086\/652701","article-title":"Safety and cross-reactive immunogenicity of candidate AS03-adjuvanted prepandemic H5N1 influenza vaccines: a randomized controlled phase 1\/2 trial in adults","volume":"201","author":"Langley","year":"2010","journal-title":"J Infect Dis"},{"key":"2020081009571917800_OFU091C12","article-title":"HHS funds the advanced development of vaccines against the H5N1 influenza strain","author":"Department of Health and Human Services","year":"2007"},{"key":"2020081009571917800_OFU091C13","article-title":"for the NVAC Subcommittee on Vaccine Development and Supply. 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