Neutralizing antibody immune correlates in COVAIL trial recipients of an mRNA second COVID-19 vaccine boost

Bo Zhang, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Youyi Fong, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Lauren Dang, Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Jonathan Fintzi, Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Shiyu Chen, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Jing Wang, Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
Nadine G. Rouphael, Hope Clinic, Emory University, Decatur, GA, USA.
Angela R. Branche, Vaccine and Treatment Evaluation Unit, University of Rochester, Rochester, NY, USA.
David J. Diemert, George Washington Vaccine Research Unit, George Washington University, Washington, DC, USA.
Ann R. Falsey, Vaccine and Treatment Evaluation Unit, University of Rochester, Rochester, NY, USA.
Daniel S. Graciaa, Hope Clinic, Emory University, Decatur, GA, USA.
Lindsey R. Baden, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Sharon E. Frey, Center for Vaccine Development, Saint Louis University, St Louis, MO, USA.
Jennifer A. Whitaker, Department of Molecular Virology and Microbiology and Department of Medicine, Baylor College of Medicine, Houston, TX, USA.
Susan J. Little, Division of Infectious Diseases and Global Public Health, Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
Satoshi Kamidani, Center for Childhood Infections and Vaccines, Children's Healthcare of Atlanta, Atlanta, GA, USA.
Emmanuel B. Walter, Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA.
Richard M. Novak, Project WISH, University of Illinois at Chicago, Chicago, IL, USA.
Richard Rupp, Department of Pediatrics, University of Texas Medical Branch, Galveston, TX, USA.
Lisa A. Jackson, Kaiser Permanente Washington Health Research Institute, Seattle, WA, USA.
Chenchen Yu, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Craig A. Magaret, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Cindy Molitor, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Bhavesh Borate, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Sydney Busch, Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA, USA.
David Benkeser, Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA, USA.
Antonia Netzl, Center for Pathogen Evolution, Department of Zoology, University of Cambridge, Cambridge, UK.
Derek J. Smith, Center for Pathogen Evolution, Department of Zoology, University of Cambridge, Cambridge, UK.
Tara M. Babu, Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, WA, USA.
Angelica C. Kottkamp, Vaccine and Treatment Evaluation Unit, Manhattan Research Clinic, New York University Grossman School of Medicine, New York, NY, USA.
Anne F. Luetkemeyer, Division of HIV, Infectious Diseases and Global Medicine, Zuckerberg San Francisco General Hospital, University of California, San Francisco, CA, USA.
Lilly C. Immergluck, Clinical Research Center, Department of Microbiology, Biochemistry, and Immunology, Morehouse School of Medicine, Atlanta, GA, USA.

Document Type

Journal Article

Publication Date

1-17-2025

Journal

Nature communications

Volume

16

Issue

1

DOI

10.1038/s41467-025-55931-w

Abstract

Neutralizing antibody titer has been a surrogate endpoint for guiding COVID-19 vaccine approval and use, although the pandemic's evolution and the introduction of variant-adapted vaccine boosters raise questions as to this surrogate's contemporary performance. For 985 recipients of an mRNA second bivalent or monovalent booster containing various Spike inserts [Prototype (Ancestral), Beta, Delta, and/or Omicron BA.1 or BA.4/5] in the COVAIL trial (NCT05289037), titers against 5 strains were assessed as correlates of risk of symptomatic COVID-19 ("COVID-19") and as correlates of relative (Pfizer-BioNTech Omicron vs. Prototype) booster protection against COVID-19 over 6 months of follow-up during the BA.2-BA.5 Omicron-dominant period. Consistently across the Moderna and Pfizer-BioNTech vaccine platforms and across all variant Spike inserts assessed, both peak and exposure-proximal ("predicted-at-exposure") titers correlated with lower Omicron COVID-19 risk in individuals previously infected with SARS-CoV-2, albeit significantly less so in naïve individuals [e.g., exposure-proximal hazard ratio per 10-fold increase in BA.1 titer 0.74 (95% CI 0.59, 0.94) for naïve vs. 0.41 (95% CI 0.23, 0.64) for non-naïve; interaction p = 0.013]. Neutralizing antibody titer was a strong inverse correlate of Omicron COVID-19 in non-naïve individuals and a weaker correlate in naïve individuals, posing questions about how prior infection alters the neutralization correlate.

Department

Medicine

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