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Immunization with inactivated whole virus particle influenza virus vaccines improves the humoral response landscape in cynomolgus macaques

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Title: Immunization with inactivated whole virus particle influenza virus vaccines improves the humoral response landscape in cynomolgus macaques
Authors: Chua, Brendon Y. Browse this author
Sekiya, Toshiki Browse this author
Koutsakos, Marios Browse this author
Nomura, Naoki Browse this author
Rowntree, Louise C. Browse this author
Nguyen, Thi H. O. Browse this author
McQuilten, Hayley A. Browse this author
Ohno, Marumi Browse this author →KAKEN DB
Ohara, Yuki Browse this author
Nishimura, Tomohiro Browse this author
Endo, Masafumi Browse this author
Itoh, Yasushi Browse this author
Habel, Jennifer R. Browse this author
Selva, Kevin J. Browse this author
Wheatley, Adam K. Browse this author
Wines, Bruce D. Browse this author
Hogarth, P. Mark Browse this author
Kent, Stephen J. Browse this author
Chung, Amy W. Browse this author
Jackson, David C. Browse this author
Brown, Lorena E. Browse this author
Shingai, Masashi Browse this author →KAKEN DB
Kedzierska, Katherine Browse this author
Kida, Hiroshi Browse this author →KAKEN DB
Issue Date: 7-Oct-2022
Publisher: PLOS
Journal Title: PLoS pathogens
Volume: 18
Issue: 10
Start Page: e1010891
Publisher DOI: 10.1371/journal.ppat.1010891
Abstract: 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-naive 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. Naive 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 gamma R2a and Fc gamma R3a 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-gamma-producing CD4(+) 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-naive individuals and also in the event of a pandemic outbreak.
Type: article
Appears in Collections:人獣共通感染症国際共同研究所 (International Institute for Zoonosis Control) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

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