Immunogenicity and safety of heterologous Omicron BA.1 and bivalent SARS-CoV-2 recombinant spike protein booster vaccines: a phase 3, randomized, clinical trial

Chijioke Bennett; E Joy Rivers; Wayne Woo; Mark Bloch; King Cheung; Paul Griffin; Rahul Mohan; Sachin Deshmukh; Mark Arya; Oscar Cumming; A Munro Neville; Toni McCallum Pardey; Joyce S Plested; Shane Cloney-Clark; Mingzhu Zhu; Raj Kalkeri; Nita Patel; Agi Buchanan; Alex Marcheschi; Jennifer Swan; Gale Smith; Iksung Cho; Gregory M Glenn; Robert Walker; Raburn M Mallory

doi:10.1093/infdis/jiad508

Immunogenicity and safety of heterologous Omicron BA.1 and bivalent SARS-CoV-2 recombinant spike protein booster vaccines: a phase 3, randomized, clinical trial

J Infect Dis. 2023 Nov 16:jiad508. doi: 10.1093/infdis/jiad508. Online ahead of print.

Authors

Chijioke Bennett¹, E Joy Rivers², Wayne Woo², Mark Bloch³, King Cheung⁴, Paul Griffin⁵, Rahul Mohan⁶, Sachin Deshmukh⁷, Mark Arya⁸, Oscar Cumming⁹, A Munro Neville¹⁰, Toni McCallum Pardey⁹, Joyce S Plested², Shane Cloney-Clark², Mingzhu Zhu², Raj Kalkeri², Nita Patel², Agi Buchanan², Alex Marcheschi², Jennifer Swan², Gale Smith², Iksung Cho², Gregory M Glenn², Robert Walker², Raburn M Mallory²

Affiliations

¹ Novavax, Inc., Gaithersburg, MD, 20878, USA.
² Novavax, Inc., Gaithersburg, MD 20878, USA.
³ Holdsworth House Medical Practice, Sydney, AU and Kirby Institute, University of New South Wales, Sydney, AU.
⁴ Emeritus Research, Camberwell, AU.
⁵ Mater Misericordiae Ltd and University of Queensland, South Brisbane, AU.
⁶ Paratus Clinical Research Western Sydney, Blacktown, AU.
⁷ Griffith University, Southport, AU.
⁸ Australian Clinical Research Network (ACRN), Anzac Parade Maroubra, AU.
⁹ Novatrials, Newcastle, AU.
¹⁰ AusTrials, Brisbane, AU.

PMID: 37970668
DOI: 10.1093/infdis/jiad508

Abstract

Background: Mutations present in emerging SARS-CoV-2 variants permit evasion of neutralization with prototype vaccines. A novel Omicron BA.1 subvariant-specific vaccine (NVX-CoV2515) was tested alone, or as a bivalent preparation in combination with the prototype vaccine (NVX-CoV2373), to assess antibody responses to SARS-CoV-2.

Methods: Participants aged 18 to 64 years immunized with 3 doses of prototype mRNA vaccines were randomized 1:1:1 to receive a single dose of NVX-CoV2515, NVX-CoV2373, or bivalent mixture in a phase 3 study investigating heterologous boosting with SARS-CoV-2 recombinant spike protein vaccines. Immunogenicity was measured 14 and 28 days after vaccination for the SARS-CoV-2 Omicron BA.1 sublineage and ancestral strain. Safety profiles of vaccines were assessed.

Results: Of participants who received trial vaccine (N = 829), those administered NVX-CoV2515 (n = 286) demonstrated superior neutralizing antibody response to BA.1 versus NVX-CoV2373 (n = 274) at Day 14 (geometric mean titer ratio [95% CI]: 1.6 [1.33, 2.03]). Seroresponse rates [n/N; 95% CI] were 73.4% [91/124; 64.7, 80.9] for NVX-CoV2515 versus 50.9% [59/116; 41.4, 60.3] for NVX-CoV2373. All formulations were similarly well-tolerated.

Conclusions: NVX-CoV2515 elicited a superior neutralizing antibody response against the Omicron BA.1 subvariant compared with NVX-CoV2373 when administered as a fourth dose. Safety data were consistent with the established safety profile of NVX-CoV2373.

Keywords: NVX-CoV2373; Omicron BA.1; SARS-CoV-2; bivalent vaccine; monovalent vaccine; neutralizing antibody; reactogenicity; seroresponse rate.