tetano
Editor, Senior Moderator
PLoS Pathog
. 2022 Oct 7;18(10):e1010891.
doi: 10.1371/journal.ppat.1010891. Online ahead of print.
Immunization with inactivated whole virus particle influenza virus vaccines improves the humoral response landscape in cynomolgus macaques
Brendon Y Chua[SUP] 1 2 [/SUP], Toshiki Sekiya[SUP] 1 2 3 [/SUP], Marios Koutsakos[SUP] 2 [/SUP], Naoki Nomura[SUP] 3 [/SUP], Louise C Rowntree[SUP] 2 [/SUP], Thi H O Nguyen[SUP] 2 [/SUP], Hayley A McQuilten[SUP] 2 [/SUP], Marumi Ohno[SUP] 3 [/SUP], Yuki Ohara[SUP] 4 [/SUP], Tomohiro Nishimura[SUP] 4 [/SUP], Masafumi Endo[SUP] 4 [/SUP], Yasushi Itoh[SUP] 5 [/SUP], Jennifer R Habel[SUP] 2 [/SUP], Kevin J Selva[SUP] 2 [/SUP], Adam K Wheatley[SUP] 2 [/SUP], Bruce D Wines[SUP] 6 7 8 [/SUP], P Mark Hogarth[SUP] 6 7 8 [/SUP], Stephen J Kent[SUP] 2 9 [/SUP], Amy W Chung[SUP] 2 [/SUP], David C Jackson[SUP] 1 2 [/SUP], Lorena E Brown[SUP] 1 2 [/SUP], Masashi Shingai[SUP] 1 3 [/SUP], Katherine Kedzierska[SUP] 1 2 [/SUP], Hiroshi Kida[SUP] 1 3 [/SUP]
Affiliations
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.
. 2022 Oct 7;18(10):e1010891.
doi: 10.1371/journal.ppat.1010891. Online ahead of print.
Immunization with inactivated whole virus particle influenza virus vaccines improves the humoral response landscape in cynomolgus macaques
Brendon Y Chua[SUP] 1 2 [/SUP], Toshiki Sekiya[SUP] 1 2 3 [/SUP], Marios Koutsakos[SUP] 2 [/SUP], Naoki Nomura[SUP] 3 [/SUP], Louise C Rowntree[SUP] 2 [/SUP], Thi H O Nguyen[SUP] 2 [/SUP], Hayley A McQuilten[SUP] 2 [/SUP], Marumi Ohno[SUP] 3 [/SUP], Yuki Ohara[SUP] 4 [/SUP], Tomohiro Nishimura[SUP] 4 [/SUP], Masafumi Endo[SUP] 4 [/SUP], Yasushi Itoh[SUP] 5 [/SUP], Jennifer R Habel[SUP] 2 [/SUP], Kevin J Selva[SUP] 2 [/SUP], Adam K Wheatley[SUP] 2 [/SUP], Bruce D Wines[SUP] 6 7 8 [/SUP], P Mark Hogarth[SUP] 6 7 8 [/SUP], Stephen J Kent[SUP] 2 9 [/SUP], Amy W Chung[SUP] 2 [/SUP], David C Jackson[SUP] 1 2 [/SUP], Lorena E Brown[SUP] 1 2 [/SUP], Masashi Shingai[SUP] 1 3 [/SUP], Katherine Kedzierska[SUP] 1 2 [/SUP], Hiroshi Kida[SUP] 1 3 [/SUP]
Affiliations
- PMID: 36206307
- 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-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.