In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 18, No. 10 ( 2022-10-7), p. e1010891-
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.
Type of Medium:
Online Resource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1010891
DOI:
10.1371/journal.ppat.1010891.g001
DOI:
10.1371/journal.ppat.1010891.g002
DOI:
10.1371/journal.ppat.1010891.g003
DOI:
10.1371/journal.ppat.1010891.g004
DOI:
10.1371/journal.ppat.1010891.g005
DOI:
10.1371/journal.ppat.1010891.g006
DOI:
10.1371/journal.ppat.1010891.s001
DOI:
10.1371/journal.ppat.1010891.s002
DOI:
10.1371/journal.ppat.1010891.s003
DOI:
10.1371/journal.ppat.1010891.s004
DOI:
10.1371/journal.ppat.1010891.s005
DOI:
10.1371/journal.ppat.1010891.s006
DOI:
10.1371/journal.ppat.1010891.s007
DOI:
10.1371/journal.ppat.1010891.s008
DOI:
10.1371/journal.ppat.1010891.s009
DOI:
10.1371/journal.ppat.1010891.s010
DOI:
10.1371/journal.ppat.1010891.s011
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2022
detail.hit.zdb_id:
2205412-1
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