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Clinical Trial
. 2025 Jun;155(6):2063-2074.e6.
doi: 10.1016/j.jaci.2025.03.015. Epub 2025 Mar 26.

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

Jeffrey M Adelglass  1 , Paul Bradley  2 , Miranda R Cai  3 , Gordon Chau  3 , Raj Kalkeri  3 , Shane Cloney-Clark  3 , Mingzhu Zhu  3 , Zhaohui Cai  3 , Mark Eickhoff  3 , Joyce S Plested  3 , Raburn M Mallory  3 , Lisa M Dunkle  4
Affiliations
Free article
Clinical Trial

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

Jeffrey M Adelglass et al. J Allergy Clin Immunol. 2025 Jun.
Free article

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.

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Conflict of interest statement

Disclosure statement This study was funded by Novavax, Inc. Disclosure of potential conflict of interest: J. M. Adelglass and P. Bradley are investigators in the 2019nCoV-312 study. J. M. Adelglass is also an investigator in COVID vaccine studies with GSK, Moderna, Inc, Pfizer Inc, Medicago Inc, and CyanVac LLC. M. R. Cai, G. Chau, R. Kalkeri, S. Cloney-Clark, M. Zhu, Z. Cai, M. Eickhoff, J. S. Plested, R. M. Mallory, and L. M. Dunkle are current employees or consultants at Novavax, Inc, and may hold stock in the company.

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