{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T05:52:29Z","timestamp":1790142749307,"version":"4.0.1"},"reference-count":21,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2015,2,5]],"date-time":"2015-02-05T00:00:00Z","timestamp":1423094400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004330","name":"GlaxoSmithKline","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004330","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Influenza Resp Viruses"],"published-print":{"date-parts":[[2015,3]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>An <jats:styled-content style=\"fixed-case\">AS<\/jats:styled-content>03\u2010adjuvanted H5N1 influenza vaccine elicited broad and persistent immune responses with an acceptable safety profile up to 6\u00a0months following the first vaccination in children aged 3\u20139\u00a0years.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this follow\u2010up of the Phase <jats:styled-content style=\"fixed-case\">II<\/jats:styled-content> study, we report immunogenicity persistence and safety at 24\u00a0months post\u2010vaccination in children aged 3\u20139\u00a0years. The randomized, open\u2010label study assessed two doses of H5N1 A\/Vietnam\/1194\/2004 influenza vaccine (1\u00b79\u00a0\u03bcg or 3\u00b775\u00a0\u03bcg hemagglutinin antigen) formulated with <jats:styled-content style=\"fixed-case\">AS<\/jats:styled-content>03<jats:sub>A<\/jats:sub> or AS03<jats:sub>B<\/jats:sub> (11\u00b789\u00a0mg or 5\u00b793\u00a0mg tocopherol, respectively). Control groups received seasonal trivalent influenza vaccine. Safety was assessed prospectively and included potential immune\u2010mediated diseases (<jats:styled-content style=\"fixed-case\">pIMD<\/jats:styled-content>s). Immunogenicity was assessed by hemagglutination\u2010inhibition assay 12 and 24\u00a0months after vaccination; cross\u2010reactivity and cell\u2010mediated responses were also assessed. (NCT00502593).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The safety population included 405 children. Over 24\u00a0months, five events fulfilled the criteria for <jats:styled-content style=\"fixed-case\">pIMD<\/jats:styled-content>s, of which four occurred in H5N1 vaccine recipients, including uveitis (<jats:italic>n<\/jats:italic>\u00a0=\u00a01) and autoimmune hepatitis (<jats:italic>n<\/jats:italic>\u00a0=\u00a01), which were considered to be vaccine\u2010related. Overall, safety profiles of the vaccines were clinically acceptable. Humoral immune responses at 12 and 24\u00a0months were reduced versus those observed after the second dose of vaccine, although still within the range of those observed after the first dose. Persistence of cell\u2010mediated immunity was strong, and <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>4<jats:sup>+<\/jats:sup> T cells with a T<jats:sub>H<\/jats:sub>1 profile were observed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Two doses of an <jats:styled-content style=\"fixed-case\">AS<\/jats:styled-content>03\u2010adjuvanted H5N1 influenza vaccine in children showed low but persistent humoral immune responses and a strong persistence of cell\u2010mediated immunity, with clinically acceptable safety profiles up to 24\u00a0months following first vaccination.<\/jats:p><\/jats:sec>","DOI":"10.1111\/irv.12295","type":"journal-article","created":{"date-parts":[[2015,2,5]],"date-time":"2015-02-05T05:29:06Z","timestamp":1423114146000},"page":"68-77","source":"Crossref","is-referenced-by-count":19,"title":["Phase <scp>II<\/scp>, randomized, open, controlled study of <scp>AS<\/scp>03\u2010adjuvanted H5N1 pre\u2010pandemic influenza vaccine in children aged 3 to 9\u00a0years: follow\u2010up of safety and immunogenicity persistence at 24\u00a0months post\u2010vaccination"],"prefix":"10.1111","volume":"9","author":[{"given":"Javier","family":"D\u00edez\u2010Domingo","sequence":"first","affiliation":[{"name":"FISABIO\u2010Public Health Valencia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9\u2010Mar\u00eda","family":"Bald\u00f3","sequence":"additional","affiliation":[{"name":"Centro de Salud Quart de Poblet Valencia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Victoria","family":"Planelles\u2010Catarino","sequence":"additional","affiliation":[{"name":"Centro de Salud Paiporta Valencia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Garc\u00e9s\u2010S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Centro de Salud Nazaret Valencia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Ubeda","sequence":"additional","affiliation":[{"name":"Centro de Salud la Eliana Valencia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angels","family":"Jubert\u2013Rosich","sequence":"additional","affiliation":[{"name":"Centro de Salud Malvarrosa Valencia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josep","family":"Mar\u00e8s","sequence":"additional","affiliation":[{"name":"Institut Pedi\u00e0tric Mar\u00e8s Riera Blanes Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pilar","family":"Garcia\u2010Corbeira","sequence":"additional","affiliation":[{"name":"GSK Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Moris","sequence":"additional","affiliation":[{"name":"GSK Vaccines Wavre Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurice","family":"Teko","sequence":"additional","affiliation":[{"name":"Clinics Waterloo Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carline","family":"Vanden Abeele","sequence":"additional","affiliation":[{"name":"GSK Vaccines Wavre Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Gillard","sequence":"additional","affiliation":[{"name":"GSK Vaccines Wavre Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,2,5]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwp237"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(08)70232-9"},{"key":"e_1_2_10_4_1","unstructured":"Food and Drug Administration.FDA approves first adjuvanted vaccine for prevention of H5N1 avian influenza. 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