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The antigenic evolution of the A(H5) hemagglutinin (HA) poses challenges for pandemic preparedness and vaccine design. Here, the global antigenic evolution of the A(H5) HA was captured in a high-resolution antigenic map. The map was used to engineer immunogenic and antigenically central vaccine HA antigens, eliciting antibody responses that broadly cover the A(H5) antigenic space. In ferrets, a central antigen protected as well as homologous vaccines against heterologous infection with two antigenically distinct viruses. This work showcases the rational design of subtype-wide influenza A(H5) pre-pandemic vaccines and demonstrates the value of antigenic maps for the evaluation of vaccine-induced immune responses through antibody profiles.<\/jats:p>","DOI":"10.1101\/2024.08.06.606696","type":"posted-content","created":{"date-parts":[[2024,8,7]],"date-time":"2024-08-07T00:00:33Z","timestamp":1722988833000},"source":"Crossref","is-referenced-by-count":3,"title":["A vaccine antigen central in influenza A(H5) virus antigenic space confers subtype-wide immunity"],"prefix":"10.64898","author":[{"given":"Adinda","family":"Kok","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samuel H.","family":"Wilks","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sina","family":"Tureli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah L.","family":"James","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Theo M.","family":"Bestebroer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David F.","family":"Burke","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mathis","family":"Funk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"van der Vliet","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monique I.","family":"Spronken","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Willemijn F.","family":"Rijnink","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Pattinson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dennis","family":"de Meulder","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miruna E.","family":"Rosu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pascal","family":"Lexmond","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Judith M.A.","family":"van den Brand","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9866-8903","authenticated-orcid":false,"given":"Sander","family":"Herfst","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Derek J.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ron A.M.","family":"Fouchier","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mathilde","family":"Richard","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2024080813300520000_2024.08.06.606696v1.1","doi-asserted-by":"publisher","DOI":"10.1007\/82_2014_396"},{"key":"2024080813300520000_2024.08.06.606696v1.2","first-page":"1152","volume-title":"Orthomyxoviridae","volume":"6","year":"2013"},{"key":"2024080813300520000_2024.08.06.606696v1.3","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1016\/j.chom.2024.05.018","article-title":"H19 influenza A virus exhibits species-specific MHC class II receptor usage","volume":"32","year":"2024","journal-title":"Cell Host Microbe"},{"key":"2024080813300520000_2024.08.06.606696v1.4","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1999.9820"},{"key":"2024080813300520000_2024.08.06.606696v1.5","doi-asserted-by":"publisher","DOI":"10.1038\/39218"},{"key":"2024080813300520000_2024.08.06.606696v1.6","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1038\/s41586-023-06631-2","article-title":"The episodic resurgence of highly pathogenic avian influenza H5 virus","volume":"622","year":"2023","journal-title":"Nature"},{"key":"2024080813300520000_2024.08.06.606696v1.7","doi-asserted-by":"crossref","unstructured":"A. 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