Nature Communications (Sep 2024)
Omicron COVID-19 immune correlates analysis of a third dose of mRNA-1273 in the COVE trial
- Bo Zhang,
- Youyi Fong,
- Jonathan Fintzi,
- Eric Chu,
- Holly E. Janes,
- Avi Kenny,
- Marco Carone,
- David Benkeser,
- Lars W. P. van der Laan,
- Weiping Deng,
- Honghong Zhou,
- Xiaowei Wang,
- Yiwen Lu,
- Chenchen Yu,
- Bhavesh Borate,
- Haiyan Chen,
- Isabel Reeder,
- Lindsay N. Carpp,
- Christopher R. Houchens,
- Karen Martins,
- Lakshmi Jayashankar,
- Chuong Huynh,
- Carl J. Fichtenbaum,
- Spyros Kalams,
- Cynthia L. Gay,
- Michele P. Andrasik,
- James G. Kublin,
- Lawrence Corey,
- Kathleen M. Neuzil,
- Frances Priddy,
- Rituparna Das,
- Bethany Girard,
- Hana M. El Sahly,
- Lindsey R. Baden,
- Thomas Jones,
- Ruben O. Donis,
- Richard A. Koup,
- Peter B. Gilbert,
- Dean Follmann,
- On behalf of the United States Government (USG) COVID-19 Immune Assays Team,
- Moderna, Inc. Team,
- Coronavirus Vaccine Prevention Network (CoVPN)/Coronavirus Efficacy (COVE) Team,
- USG/CoVPN Biostatistics Team
Affiliations
- Bo Zhang
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
- Youyi Fong
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
- Jonathan Fintzi
- Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Eric Chu
- Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research
- Holly E. Janes
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
- Avi Kenny
- Department of Biostatistics, University of Washington
- Marco Carone
- Department of Biostatistics, University of Washington
- David Benkeser
- Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University
- Lars W. P. van der Laan
- Department of Statistics, University of Washington
- Weiping Deng
- Moderna, Inc
- Honghong Zhou
- Moderna, Inc
- Xiaowei Wang
- Moderna, Inc
- Yiwen Lu
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
- Chenchen Yu
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
- Bhavesh Borate
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
- Haiyan Chen
- Biomedical Advanced Research and Development Authority
- Isabel Reeder
- Biomedical Advanced Research and Development Authority
- Lindsay N. Carpp
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
- Christopher R. Houchens
- Biomedical Advanced Research and Development Authority
- Karen Martins
- Biomedical Advanced Research and Development Authority
- Lakshmi Jayashankar
- Biomedical Advanced Research and Development Authority
- Chuong Huynh
- Biomedical Advanced Research and Development Authority
- Carl J. Fichtenbaum
- Division of Infectious Diseases, Department of Medicine, University of Cincinnati
- Spyros Kalams
- Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center
- Cynthia L. Gay
- Department of Medicine, Division of Infectious Diseases, UNC HIV Cure Center, University of North Carolina at Chapel Hill School of Medicine
- Michele P. Andrasik
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
- James G. Kublin
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
- Lawrence Corey
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
- Kathleen M. Neuzil
- Center for Vaccine Development and Global Health, University of Maryland School of Medicine
- Frances Priddy
- Moderna, Inc
- Rituparna Das
- Moderna, Inc
- Bethany Girard
- Moderna, Inc
- Hana M. El Sahly
- Department of Molecular Virology and Microbiology, Baylor College of Medicine
- Lindsey R. Baden
- Brigham and Women’s Hospital
- Thomas Jones
- Biomedical Advanced Research and Development Authority
- Ruben O. Donis
- Biomedical Advanced Research and Development Authority
- Richard A. Koup
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Peter B. Gilbert
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
- Dean Follmann
- Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- On behalf of the United States Government (USG) COVID-19 Immune Assays Team
- Moderna, Inc. Team
- Coronavirus Vaccine Prevention Network (CoVPN)/Coronavirus Efficacy (COVE) Team
- USG/CoVPN Biostatistics Team
- DOI
- https://doi.org/10.1038/s41467-024-52348-9
- Journal volume & issue
-
Vol. 15,
no. 1
pp. 1 – 13
Abstract
Abstract In the phase 3 Coronavirus Efficacy (COVE) trial (NCT04470427), post-dose two Ancestral Spike-specific binding (bAb) and neutralizing (nAb) antibodies were shown to be correlates of risk (CoR) and of protection against Ancestral-lineage COVID-19 in SARS-CoV-2 naive participants. In the SARS-CoV-2 Omicron era, Omicron subvariants with varying degrees of immune escape now dominate, seropositivity rates are high, and booster doses are administered, raising questions on whether and how these developments affect the bAb and nAb correlates. To address these questions, we assess post-boost BA.1 Spike-specific bAbs and nAbs as CoRs and as correlates of booster efficacy in COVE. For naive individuals, bAbs and nAbs inversely correlate with Omicron COVID-19: hazard ratios (HR) per 10-fold marker increase (95% confidence interval) are 0.16 (0.03, 0.79) and 0.31 (0.10, 0.96), respectively. In non-naive individuals the analogous results are similar: 0.15 (0.04, 0.63) and 0.28 (0.07, 1.08). For naive individuals, three vs two-dose booster efficacy correlates with predicted nAb titer at exposure, with estimates -8% (-126%, 48%), 50% (25%, 67%), and 74% (49%, 87%), at 56, 251, and 891 Arbitrary Units/ml. These results support the continued use of antibody as a surrogate endpoint.
