| Autor: |
Brendon Chua, Toshiki Sekiya, Marios Koutsakos, Naoki Nomura, Louise Rowntree, Thi Nguyen, Hayley McQuilten, Marumi Ohno, Yuki Ohara, Tomohiro Nishimura, Masafumi Endo, Yasushi Itoh, Jennifer Habel, Kevin Selva, Adam Wheatley, Bruce Wines, P. Mark Hogarth, Stephen Kent, Amy Chung, David Jackson, Lorena Brown, Masashi Shingai, Katherine Kedzierska, Hiroshi Kida |
| Rok vydání: |
2022 |
| DOI: |
10.21203/rs.3.rs-1390960/v1 |
| Popis: |
Influenza viruses circulate globally, causing seasonal influenza outbreaks. Although antibody-inducing vaccines are the most effective way to combat seasonal infections, current vaccines can have poor efficacy, especially in children and immunocompromised individuals. We investigated the immunogenicity and efficacy of monovalent and quadrivalent formulations of the whole virus particle vaccine (WPV) in comparison to the commonly used split vaccines (SVs) in a non-human primate model. Naïve cynomolgus macaques vaccinated with either monovalent or quadrivalent WPV formulations consistently induced a stronger neutralizing antibody response against vaccine-matched virus strains, while reactogenicity was minimal. In contrast to the modest responses in SV-vaccinated animals, responses in WPV-primed animals were further increased by boosting with either formulation. Using a 28-parameter multiplex bead array to define key antibody features, we found that while both WPV and SV induced elevated IgG responses against A/H1N1 nucleoprotein, only WPV elevated IgG responses against A/H1N1 haemagglutinin (HA) and HA-Stem after each vaccine dose. Higher IgA responses to A/H1N1-HA were also induced after each WPV dose. Antibodies to A/H1N1-HA and HA-Stem that could engage FcγR2a and FcγR3a were present at higher levels after one dose of WPV compared to SV and remained elevated after the second dose. WPV-enhanced antibody responses were associated with higher frequencies of HA-reactive B-cells and IFN-γ-producing CD4+ T-cell responses. Our data suggest that robust antibody responses require WPV to be given as a priming dose but do not depend on the vaccine type used for the second dose. In contrast, antibody responses are not as prominent when SV is given first. Our findings support vaccination regimens using WPV, which may be particularly beneficial for priming immunologically-naïve individuals, such as the young and immunocompromised, and also advantageous in the event of a pandemic outbreak. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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