Effect of Omicron BA.1-based compared to prototype booster mRNA vaccination on incidence of COVID-19 in the COVAIL trial

Authors

• David J. Diemert, Department of Medicine, School of Medicine and Health Sciences, The George Washington University, Washington, DC, USA. Electronic address: ddiemert@gwu.edu.
• Daniel S. Graciaa, Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Emory University School of Medicine, Decatur, GA, USA.
• Bo Zhang, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA.
• Nadine G. Rouphael, Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Emory University School of Medicine, Decatur, GA, USA.
• Angela R. Branche, Vaccine and Treatment Evaluation Unit, University of Rochester, Rochester, New York, USA.
• Thomas C. Martin, University of California, San Diego, La Jolla, California, USA.
• Lisa A. Jackson, Kaiser Permanente Washington Health Research Institute, Seattle, Washington, USA.
• Rachel M. Presti, Department of Medicine, Washington University School of Medicine, St Louis, MO, USA.
• Satoshi Kamidani, Center for Childhood Infections and Vaccines, Children's Healthcare of Atlanta, GA, USA; Department of Pediatrics, Emory University, Atlanta, GA, USA.
• Siham M. Mahgoub, Howard University College of Medicine, Howard University Hospital, Washington, DC, USA.
• Tara M. Babu, Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, Washington, USA.
• Craig A. Magaret, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA.
• Viviana Simon, Department of Microbiology, Icahn School of Medicine at Mount Sinai, NY, New York, USA; Center for Vaccine Research and Pandemic Preparedness (C-VaRPP), Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Pathology, Molecular and Cell Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Division of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA; The Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
• Harm van Bakel, Department of Microbiology, Icahn School of Medicine at Mount Sinai, NY, New York, USA; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Artificial Intelligence and Human Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Icahn Genomics Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
• Paul C. Roberts, Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
• John H. Beigel, Center for Vaccine Research and Pandemic Preparedness (C-VaRPP), Icahn School of Medicine at Mount Sinai, New York, NY, USA.
• Peter B. Gilbert, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA; Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA; Department of Biostatistics, School of Public Health, University of Washington, Seattle, Washington, USA.
• Dean Follmann, Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

Document Type

Journal Article

Publication Date

9-9-2025

Journal

Vaccine

Volume

64

DOI

10.1016/j.vaccine.2025.127718

Keywords

COVID-19; SARS-CoV-2; Vaccine efficacy; Variant; mRNA vaccine

Abstract

BACKGROUND: Covid-19 vaccines are updated to match circulating strains based on reasoning that better strain-matched immunogenicity should provide better protection. Randomized evidence with disease endpoints to support strain matching is lacking. We evaluated COVID-19 incidence among adults randomized to a second booster of Prototype or Omicron-based vaccines. METHODS: COVAIL was a four-stage Phase 2 clinical trial; results from Stages 1 (mRNA-1273 [Moderna]) and 2 (BNT162b2 [Pfizer/BioNTech]) are described here. Adults who had received a primary series and one booster of an authorized COVID-19 vaccine were eligible. Participants received one dose of either Prototype vaccine or a monovalent or bivalent Omicron BA.1 vaccine. SARS-CoV-2 neutralization titers (ID) were measured pre- and post-vaccination. Covariate-adjusted cumulative COVID-19 incidence and Cox regression analyses were conducted separately for each stage. RESULTS: 706 participants with pre- and day 15 post-vaccination ID titers (n = 503 in Stage 1, n = 203 in Stage 2) were included. Within stages, participant characteristics and baseline ID titers were similar between Prototype and Omicron-based arms. There was no difference in cumulative COVID-19 incidence for Prototype vs. Omicron-based vaccine in Stage 1 (RR 1.04, 95 % CI 0.73-1.48), while incidence was higher among Prototype recipients in Stage 2 (RR 2.56, 1.44-4.52). Cox regression analysis showed no difference in Stage 1 (HR 1.04, 0.68-1.58), but higher incidence for Prototype recipients in Stage 2 (HR 2.95, 1.52-5.72). CONCLUSIONS: Omicron-based vaccines as second boosters were more protective against COVID-19 relative to Prototype among those receiving BNT162b2 but not mRNA-1273. Differences between stages such as force of infection, antigen matching, and vaccine differences may explain this finding. CLINICALTRIALS: govRegistry Number: NCT05289037.

APA Citation

Diemert, David J.; Graciaa, Daniel S.; Zhang, Bo; Rouphael, Nadine G.; Branche, Angela R.; Martin, Thomas C.; Jackson, Lisa A.; Presti, Rachel M.; Kamidani, Satoshi; Mahgoub, Siham M.; Babu, Tara M.; Magaret, Craig A.; Simon, Viviana; van Bakel, Harm; Roberts, Paul C.; Beigel, John H.; Gilbert, Peter B.; and Follmann, Dean, "Effect of Omicron BA.1-based compared to prototype booster mRNA vaccination on incidence of COVID-19 in the COVAIL trial" (2025). GW Authored Works. Paper 7973.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/7973

Department

Medicine