PLoS Pathogens (Oct 2022)

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

  • Brendon Y Chua,
  • Toshiki Sekiya,
  • Marios Koutsakos,
  • Naoki Nomura,
  • Louise C Rowntree,
  • Thi H O Nguyen,
  • Hayley A McQuilten,
  • Marumi Ohno,
  • Yuki Ohara,
  • Tomohiro Nishimura,
  • Masafumi Endo,
  • Yasushi Itoh,
  • Jennifer R Habel,
  • Kevin J Selva,
  • Adam K Wheatley,
  • Bruce D Wines,
  • P Mark Hogarth,
  • Stephen J Kent,
  • Amy W Chung,
  • David C Jackson,
  • Lorena E Brown,
  • Masashi Shingai,
  • Katherine Kedzierska,
  • Hiroshi Kida

DOI
https://doi.org/10.1371/journal.ppat.1010891
Journal volume & issue
Vol. 18, no. 10
p. e1010891

Abstract

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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.