Immunization with inactivated whole virus particle influenza virus vaccines improves the humoral response landscape in cynomolgus macaques
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Published:2022-10-07
Issue:10
Volume:18
Page:e1010891
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ISSN:1553-7374
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Container-title:PLOS Pathogens
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language:en
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Short-container-title:PLoS Pathog
Author:
Chua Brendon Y.,
Sekiya Toshiki,
Koutsakos Marios,
Nomura Naoki,
Rowntree Louise C.,
Nguyen Thi H. O.,
McQuilten Hayley A.,
Ohno Marumi,
Ohara Yuki,
Nishimura Tomohiro,
Endo Masafumi,
Itoh Yasushi,
Habel Jennifer R.,
Selva Kevin J.,
Wheatley Adam K.,
Wines Bruce D.,
Hogarth P. Mark,
Kent Stephen J.,
Chung Amy W.,
Jackson David C.,
Brown Lorena E.,
Shingai Masashi,
Kedzierska KatherineORCID,
Kida Hiroshi
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-naïve 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. Naïve 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 FcγR2a and FcγR3a 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-γ-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-naïve individuals and also in the event of a pandemic outbreak.
Funder
Japan Initiative for Global Research Network on Infectious Diseases
Japan Program for Infectious Diseases Research and Infrastructure
Research Program on Emerging and Re-emerging Infectious Diseases
GI-CoRE Program of Hokkaido University
Doctoral Program for World-leading Innovative & Smart Education Program
JSPS KAKENHI
Australian National Health and Medical Research Council
NHMRC
Dame Kate Campbell Fellowship from The University of Melbourne
The University of Melbourne
Publisher
Public Library of Science (PLoS)
Subject
Virology,Genetics,Molecular Biology,Immunology,Microbiology,Parasitology
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