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

Authors

• 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.

APA Citation

Zhang, Bo; Fong, Youyi; Dang, Lauren; Fintzi, Jonathan; Chen, Shiyu; Wang, Jing; Rouphael, Nadine G.; Branche, Angela R.; Diemert, David J.; Falsey, Ann R.; Graciaa, Daniel S.; Baden, Lindsey R.; Frey, Sharon E.; Whitaker, Jennifer A.; Little, Susan J.; Kamidani, Satoshi; Walter, Emmanuel B.; Novak, Richard M.; Rupp, Richard; Jackson, Lisa A.; Yu, Chenchen; Magaret, Craig A.; Molitor, Cindy; Borate, Bhavesh; Busch, Sydney; Benkeser, David; Netzl, Antonia; Smith, Derek J.; Babu, Tara M.; Kottkamp, Angelica C.; Luetkemeyer, Anne F.; and Immergluck, Lilly C., "Neutralizing antibody immune correlates in COVAIL trial recipients of an mRNA second COVID-19 vaccine boost" (2025). GW Authored Works. Paper 6347.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/6347

Department

Medicine