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Current strategies involve post\u2010emergent homotypic vaccines that are modelled upon select circulating \u2018seasonal\u2019 influenzas, but cannot induce cross\u2010strain protection against newly evolved or zoonotically introduced highly pathogenic influenza (HPI). Avian H5N1 and the less\u2010lethal 2009 H1N1 and their reassortants loom as candidates to seed a future HPI pandemic. Therefore, more universal \u2018seasoned\u2019 vaccine approaches are urgently needed for heterotypic protection ahead of time. Pivotal to this is the need to understand mechanisms that can deliver broad strain protection. Heterotypic and heterosubtypic humoral immunities have largely been overlooked for influenza cross\u2010protection, with most \u2018seasoned\u2019 vaccine efforts for humans focussed on heterotypic cellular immunity. However, 5 years ago we began to identify direct and indirect indicators of humoral\u2010herd immunity to protein sites preserved among H1N1, H3N2 and H5N1 influenzas. Since then the evidence for cross\u2010protective antibodies in humans has been accumulating. Now proposed is a rationale to stimulate and enhance pre\u2010existing heterotypic humoral responses that, together with cell\u2010mediated initiatives, will deliver pre\u2010emptive and universal human protection against emerging epidemic and pandemic influenzas.<\/jats:p>","DOI":"10.1038\/icb.2011.38","type":"journal-article","created":{"date-parts":[[2011,6,7]],"date-time":"2011-06-07T09:48:45Z","timestamp":1307440125000},"page":"149-158","source":"Crossref","is-referenced-by-count":7,"title":["Seasoned adaptive antibody immunity for highly pathogenic pandemic influenza in humans"],"prefix":"10.1111","volume":"90","author":[{"given":"Garry W","family":"Lynch","sequence":"first","affiliation":[{"name":"Biosafety, Immunobiology, Global Health and Pandemic Infections Research, Central Clinical School, Faculties of Medicine, The University of Sydney  Camperdown New South Wales Australia"},{"name":"Veterinary Science, University of Sydney  Camperdown New South Wales Australia"},{"name":"Cellular &amp; Molecular Pathology Research Unit, Oral Pathology and Oral Medicine, Westmead Centre for Oral Health, Westmead Hospital and Faculty of Dentistry, University of Sydney  Westmead New South Wales Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Selleck","sequence":"additional","affiliation":[{"name":"The Australian Animal Health Laboratories, CSIRO  Geelong Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W Bret","family":"Church","sequence":"additional","affiliation":[{"name":"Group in Biomolecular Structure and Informatics, Pharmaceutical Chemistry, Faculty of Pharmacy, University of Sydney  Camperdown New South Wales Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John S","family":"Sullivan","sequence":"additional","affiliation":[{"name":"Biosafety, Immunobiology, Global Health and Pandemic Infections Research, Central Clinical School, Faculties of Medicine, The University of Sydney  Camperdown New South Wales Australia"},{"name":"Children's Cancer Institute Australia for Medical Research  Randwick New South Wales Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2011,6,7]]},"reference":[{"key":"e_1_2_11_1_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1176062"},{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMp0904819"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature08182"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2180-9-77"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0900877106"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00534-09"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0912807107"},{"key":"e_1_2_11_8_1","first-page":"1","volume-title":"Global Macroeconomic Consequences of Pandemic Influenza","author":"McKibben WJ","year":"2006"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2009.02.011"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1093373"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02162-09"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1124513"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1186430"},{"key":"e_1_2_11_14_1","first-page":"1533","volume-title":"Fields Virology","author":"Wright PF","year":"2001"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02694-07"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2010.01.053"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.2174\/092986709789104984"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.2174\/092986707779313444"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-200464180-00003"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.mi.37.100183.002525"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.323.5921.1560"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2006.01.007"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.3201\/eid1209.05-0979"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.3201\/eid1401.061283"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.89.1.170-174.1965"},{"key":"e_1_2_11_26_1","first-page":"371","article-title":"Studies of active immunogenesis in poliomyelitis. 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