Immunogenicity of adjuvanted recombinant SARS-CoV-2 spike protein vaccine after earlier mRNA vaccine doses

Abstract

Background: To support heterologous vaccine regimens, periodic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) revaccination requires immunogenicity and safety data for adjuvanted protein-based vaccines following prior mRNA doses.

Objective: We sought to assess noninferiority of neutralizing antibody (nAb) titers following a second dose versus a first dose (in a prior study) of an SARS-CoV-2 protein-based vaccine (NVX-CoV2373) administered following a primary series (2 or 3 doses) of an mRNA vaccine.

Methods: This phase 3, open-label study (2019nCoV-312/NCT05875701) enrolled participants who had received 1 dose of the ancestral SARS-CoV-2 protein-based vaccine in an earlier study (2019nCoV-307/NCT05463068) after a primary series (2 or 3 doses) of a commercial mRNA vaccine. In the current study, participants received an additional dose of protein vaccine (ancestral [n = 104] or Omicron BA.5 [n = 40]) at least 180 days after their previous study dose.

Results: The study enrolled 144 participants. The ratio of anti-Wuhan nAbs (geometric mean titer) at day 28 after this study dose (ancestral 393.2 IU/mL [95% CI 318.0-468.2]) versus previous study dose (396.6 IU/mL [95% CI 328.7-478.6]) was 1.0 (0.8-1.2), meeting noninferiority. The seroresponse rate difference between doses was 7.4% (95% CI -1.2% to 16.5%), also meeting noninferiority. Omicron BA.5 nAb titers suggest cross-protection against emerging variants. The anti-Wuhan nAb ratio at day 28 between Omicron BA.5 vaccine dose in this study (835.0 [597.1-1167.6]) versus the ancestral vaccine in the previous study (436.0 [305.6-622.2]) was 1.9 (1.5-2.5), exceeding superiority criterion. Local and systemic reactions were similar between doses and strains in both studies.

Conclusion: A heterologous regimen of 2 adjuvanted, recombinant spike protein vaccine doses following multiple mRNA vaccine doses produced robust immune responses, exhibiting cross-reactivity to some newer variants.

Keywords: COVID-19; SARS-CoV-2; cross-reactivity; neutralizing antibody; noninferior immunogenicity; seroresponse rate; vaccine.