Immune correlates analysis of the mRNA-1273 COVID-19 vaccine efficacy clinical trial

• Type of Material: Article
• Authors: Peter B Gilbert, Fred Hutchinson Cancer Research Center; David C Montefiori, Duke University; Adrian McDermott, National Institute of Allergy and Infectious Diseases, NIH, Bethesda; Youyi Fong, Fred Hutchinson Cancer Research Center; David Benkeser, Emory University; Weiping Deng, Moderna Inc; Honghong Zhou, Moderna Inc; 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; Flora Castellino, Biomedical Advanced Research and Development Authority; Britta Flach, National Institute of Allergy and Infectious Diseases, NIH, Bethesda; Bob C Lin, National Institute of Allergy and Infectious Diseases, NIH, Bethesda; Sarah O'Connell, National Institute of Allergy and Infectious Diseases, NIH, Bethesda; Charlene McDanal, Duke University; Amanda Eaton, Duke University; Marcella Sarzotti-Kelsoe, Duke University; Yiwen Lu, Fred Hutchinson Cancer Research Center; Chenchen Yu, Fred Hutchinson Cancer Research Center; Bhavesh Borate, Fred Hutchinson Cancer Research Center; Lars WP van der Laan, Fred Hutchinson Cancer Research Center; Nima Hejazi, Fred Hutchinson Cancer Research Center; Chuong Huynh, Biomed Adv Res & Dev Author; Jacqueline Miller, Moderna Inc; Hana M El Sahly, Baylor College of Medicine; Lindsey R Baden, Brigham and Women’s Hospital; Mira Baron, Palm Beach Research Center; Luis De la Cruz, Keystone Vitalink Research; Cynthia Gay, University of North Carolina Chapel Hill; Spyros Kalams, Vanderbilt University; Colleen Kelley, Emory University; Michele P Andrasik, Fred Hutchinson Cancer Research Center; James G Kublin, Fred Hutchinson Cancer Research Center; Lawrence Corey, Fred Hutchinson Cancer Research Center; Kathleen M Neuzil, University of Maryland, Baltimore; Lindsay N Carpp, Fred Hutchinson Cancer Research Center; Rolando Pajon, Moderna Inc; Dean Follmann, National Institute of Allergy and Infectious Diseases, NIH, Bethesda; Rubern O Donis, Biomedical Advanced Research and Development Authority; Richard A Koup, National Institute of Allergy and Infectious Diseases, NIH, Bethesda
• Language: English
• Date: 2022-01-07
• Publisher: AMER ASSOC ADVANCEMENT SCIENCE
• Publication Version: Final Published Version
• Copyright Statement: © 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1126/science.abm3425
• Title of Journal or Parent Work: SCIENCE
• Volume: 375
• Issue: 6576
• Start Page: 43
• End Page: +
• Grant/Funding Information: This study was supported by the Public Health Service; the National Institute of Allergy and Infectious Diseases; National Institutes of Health grant UM1AI068635 (to P.B.G.); the Office of Research Infrastructure Programs; National Institutes of Health grant (S10OD028685) (Fred Hutchinson Cancer Research Center); Moderna, Inc. Federal funds from the Office of the Assistant Secretary for Preparedness and Response; the Biomedical Advanced Research and Development Authority, contract no. 75A50120C00034 (Moderna, Inc.); and the Infectious Disease Clinical Research Consortium Leadership Group through the National Institute for Allergy and Infectious Diseases, grant UM1 AI148684-03 (to K.M.N.).
• Keywords: Multidisciplinary Sciences; PROTECTION; SENSITIVITY-ANALYSIS; Science & Technology - Other Topics; Science & Technology
• Research Categories: Health Sciences, Pathology; Biology, Biostatistics; Health Sciences, Medicine and Surgery

Abstract

In the coronavirus efficacy (COVE) phase 3 clinical trial, vaccine recipients were assessed for neutralizing and binding antibodies as correlates of risk for COVID-19 disease and as correlates of protection. These immune markers were measured at the time of second vaccination and 4 weeks later, with values reported in standardized World Health Organization international units. All markers were inversely associated with COVID-19 risk and directly associated with vaccine efficacy. Vaccine recipients with postvaccination 50% neutralization titers 10, 100, and 1000 had estimated vaccine efficacies of 78% (95% confidence interval, 54 to 89%), 91% (87 to 94%), and 96% (94 to 98%), respectively. These results help define immune marker correlates of protection and may guide approval decisions for messenger RNA (mRNA) COVID-19 vaccines and other COVID-19 vaccines.