{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T16:58:31Z","timestamp":1767891511898,"version":"3.49.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1010891","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,10,19]],"date-time":"2022-10-19T00:00:00Z","timestamp":1666137600000}}],"reference-count":49,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2022,10,7]],"date-time":"2022-10-07T00:00:00Z","timestamp":1665100800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Japan Initiative for Global Research Network on Infectious Diseases","award":["JP19fm0108008"],"award-info":[{"award-number":["JP19fm0108008"]}]},{"name":"Japan Program for Infectious Diseases Research and Infrastructure","award":["JP20wm0125008"],"award-info":[{"award-number":["JP20wm0125008"]}]},{"name":"Research Program on Emerging and Re-emerging Infectious Diseases","award":["21fk0108142"],"award-info":[{"award-number":["21fk0108142"]}]},{"name":"GI-CoRE Program of Hokkaido University"},{"name":"Doctoral Program for World-leading Innovative & Smart Education Program","award":["1801"],"award-info":[{"award-number":["1801"]}]},{"name":"JSPS KAKENHI","award":["21H02376, 17K15367, 18K07135 and 15H04720"],"award-info":[{"award-number":["21H02376, 17K15367, 18K07135 and 15H04720"]}]},{"name":"Australian National Health and Medical Research Council","award":["Grant (1071916)"],"award-info":[{"award-number":["Grant (1071916)"]}]},{"DOI":"10.13039\/501100000925","name":"NHMRC","doi-asserted-by":"crossref","award":["Senior Research Fellowship Level B (#1102792)"],"award-info":[{"award-number":["Senior Research Fellowship Level B (#1102792)"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000925","name":"NHMRC","doi-asserted-by":"crossref","award":["Investigator Grant (#1173871)"],"award-info":[{"award-number":["Investigator Grant (#1173871)"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Dame Kate Campbell Fellowship from The University of Melbourne"},{"DOI":"10.13039\/501100000925","name":"NHMRC","doi-asserted-by":"crossref","award":["Emerging Leadership Level 1 Investigator Grant #1194036"],"award-info":[{"award-number":["Emerging Leadership Level 1 Investigator Grant #1194036"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000925","name":"NHMRC","doi-asserted-by":"crossref","award":["Emerging Leadership Level 1 Investigator Grant #1195698"],"award-info":[{"award-number":["Emerging Leadership Level 1 Investigator Grant #1195698"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001782","name":"The University of Melbourne","doi-asserted-by":"crossref","award":["Melbourne Research Scholarship"],"award-info":[{"award-number":["Melbourne Research Scholarship"]}],"id":[{"id":"10.13039\/501100001782","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000925","name":"NHMRC","doi-asserted-by":"crossref","award":["Project grant (#GNT1145303)"],"award-info":[{"award-number":["Project grant (#GNT1145303)"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Although antibody-inducing split virus vaccines (SV) are currently the most effective way to combat seasonal influenza, their efficacy can be modest, especially in immunologically-na\u00efve individuals. We investigated immune responses towards inactivated whole influenza virus particle vaccine (WPV) formulations, predicated to be more immunogenic, in a non-human primate model, as an important step towards clinical testing in humans. Comprehensive analyses were used to capture 46 immune parameters to profile how WPV-induced responses differed to those elicited by antigenically-similar SV formulations. Na\u00efve cynomolgus macaques vaccinated with either monovalent or quadrivalent WPV consistently induced stronger antibody responses and hemagglutination inhibition (HI) antibody titres against vaccine-matched viruses compared to SV formulations, while acute reactogenic effects were similar. Responses in WPV-primed animals were further increased by boosting with the same formulation, conversely to modest responses after priming and boosting with SV. 28-parameter multiplex bead array defined key antibody features and showed that while both WPV and SV induced elevated IgG responses against A\/H1N1 nucleoprotein, only WPV increased IgG responses against A\/H1N1 hemagglutinin (HA) and HA-Stem, and higher IgA responses to A\/H1N1-HA after each vaccine dose. Antibodies to A\/H1N1-HA and HA-Stem that could engage Fc\u03b3R2a and Fc\u03b3R3a were also present at higher levels after one dose of WPV compared to SV and remained elevated after the second dose. Furthermore, WPV-enhanced antibody responses were associated with higher frequencies of HA-specific B-cells and IFN-\u03b3-producing CD4<jats:sup>+<\/jats:sup> T-cell responses. Our data additionally demonstrate stronger boosting of HI titres by WPV following prior infection and support WPV administered as a priming dose irrespective of the follow up vaccine for the second dose. Our findings thus show that compared to SV vaccination, WPV-induced humoral responses are significantly increased in scope and magnitude, advocating WPV vaccination regimens for priming immunologically-na\u00efve individuals and also in the event of a pandemic outbreak.<\/jats:p>","DOI":"10.1371\/journal.ppat.1010891","type":"journal-article","created":{"date-parts":[[2022,10,7]],"date-time":"2022-10-07T17:46:18Z","timestamp":1665164778000},"page":"e1010891","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["Immunization with inactivated whole virus particle influenza virus vaccines improves the humoral response landscape in cynomolgus macaques"],"prefix":"10.1371","volume":"18","author":[{"given":"Brendon Y.","family":"Chua","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshiki","family":"Sekiya","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marios","family":"Koutsakos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naoki","family":"Nomura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Louise C.","family":"Rowntree","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thi H. 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Prevalence of Influenza Antibodies\u20142021 Bulletin 2nd Report. Available from: https:\/\/www.niid.go.jp\/niid\/ja\/flu-m\/253-idsc\/yosoku\/sokuhou\/10864-flu-yosoku-rapid2021-2.html."},{"key":"ppat.1010891.ref004","volume-title":"Prevalence of Influenza Antibodies\u2014","author":"National Institute of Infectious Disease (Japan).","year":"2019"},{"key":"ppat.1010891.ref005","unstructured":"Department of Health and Aged Care (Australia). Australian Influenza Surveillance Report\u2014No 07\u2014fortnight ending 03 July 2022. 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