Beta-containing bivalent SARS-CoV-2 protein vaccine elicits durable broad neutralization in macaques and protection in hamsters

Catherine Berry; Vincent Pavot; Natalie G Anosova; Michael Kishko; Lu Li; Tim Tibbitts; Alice Raillard; Sylviane Gautheron; Sheila Cummings; Dinesh S Bangari; Swagata Kar; Caroline Atyeo; Yixiang Deng; Galit Alter; Cindy Gutzeit; Marguerite Koutsoukos; Roman M Chicz; Valerie Lecouturier

doi:10.1038/s43856-023-00302-z

Beta-containing bivalent SARS-CoV-2 protein vaccine elicits durable broad neutralization in macaques and protection in hamsters

Commun Med (Lond). 2023 May 26;3(1):75. doi: 10.1038/s43856-023-00302-z.

Authors

Catherine Berry^#¹, Vincent Pavot^#¹, Natalie G Anosova², Michael Kishko², Lu Li², Tim Tibbitts², Alice Raillard¹, Sylviane Gautheron¹, Sheila Cummings³, Dinesh S Bangari³, Swagata Kar⁴, Caroline Atyeo⁵, Yixiang Deng⁵, Galit Alter⁵, Cindy Gutzeit⁶, Marguerite Koutsoukos⁷, Roman M Chicz², Valerie Lecouturier⁸

Affiliations

¹ Sanofi, Vaccines R&D, Marcy l'Etoile, France.
² Sanofi, Vaccines R&D, Cambridge, MA, USA.
³ Sanofi, Framingham, MA, USA.
⁴ BIOQUAL Inc, Rockville, MD, USA.
⁵ Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.
⁶ GSK, Rixensart, Belgium.
⁷ GSK, Wavre, Belgium.
⁸ Sanofi, Vaccines R&D, Marcy l'Etoile, France. valerie.lecouturier@sanofi.com.

^# Contributed equally.

Abstract

Background: Since the beginning of the COVID-19 pandemic, several variants of concern (VOC) have emerged for which there is evidence of an increase in transmissibility, more severe disease, and/or reduced vaccine effectiveness. Effective COVID-19 vaccine strategies are required to achieve broad protective immunity against current and future VOC.

Methods: We conducted immunogenicity and challenge studies in macaques and hamsters using a bivalent recombinant vaccine formulation containing the SARS-CoV-2 prefusion-stabilized Spike trimers of the ancestral D614 and the variant Beta strains with AS03 adjuvant (CoV2 preS dTM-AS03) in a primary immunization setting.

Results: We show that a primary immunization with the bivalent CoV2 preS dTM-AS03 elicits broader and durable (1 year) neutralizing antibody responses against VOC including Omicron BA.1 and BA.4/5, and SARS-CoV-1 as compared to the ancestral D614 or Beta variant monovalent vaccines in naïve non-human primates. In addition, the bivalent formulation confers protection against viral challenge with SARS-CoV-2 prototype D614G strain as well as Alpha and Beta variant strains in hamsters.

Conclusions: Our findings demonstrate the potential of a Beta-containing bivalent CoV2 preS dTM-AS03 formulation to provide broad and durable immunogenicity, as well as protection against VOC in naïve populations.

Plain language summary

SARS-CoV-2 has changed over time, resulting in different forms of the virus called variants. These variants compromise the protection offered by the COVID-19 vaccines, which trigger an immune response against the viral Spike protein that allows the virus to attach and infect human cells, since their spike proteins are different. Here, we developed and tested a vaccine containing two different Spike proteins, one from the original Wuhan strain and another from the Beta variant. In macaques, the vaccine leads to the production of antibodies able to stop all variants tested from infecting human cells, including Omicron, with stable levels over one year. In hamsters, the vaccine protected against infection with the ancestral virus and the Alpha and Beta variants. Our findings have important implications for vaccine control of existing and future SARS-CoV-2 variants of concern.