Immune correlates analysis of a phase 3 trial of the AZD1222 (ChAdOx1 nCoV-19) vaccine

• Type of Material: Article
• Authors: David Benkeser, Emory University; Youyi Fong, Fred Hutchinson Cancer Research Center; Holly E Janes, Fred Hutchinson Cancer Research Center; Elizabeth J Kelly, AstraZeneca; Ian Hirsch, AstraZeneca; Stephanie Sproule, AstraZeneca; Ann Marie Stanley, AstraZeneca; Jill Maaske, AstraZeneca; Tonya Villafana, AstraZeneca; Christopher R Houchens, United States Department of Health and Human Services; Karen Martins, United States Department of Health and Human Services; Lakshmi Jayashankar, United States Department of Health and Human Services; Flora Castellino, United States Department of Health and Human Services; Victor Ayala, United States Department of Health and Human Services; Christos J Petropoulos, Monogram Biosciences; Andrew Leith, Nexelis; Deanne Haugaard, Nexelis; Bill Webb, Nexelis; 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 S Hejazi, Fred Hutchinson Cancer Research Center; Lindsay N Carpp, Fred Hutchinson Cancer Research Center; April K Randhawa, Fred Hutchinson Cancer Research Center; Michele P Andrasik, Fred Hutchinson Cancer Research Center; James G Kublin, Fred Hutchinson Cancer Research Center; Margaret Brewinski Isaacs, National Institute of Allergy and Infectious Diseases (NIAID); Mamodikoe Makhene, National Institute of Allergy and Infectious Diseases (NIAID); Tina Tong, National Institute of Allergy and Infectious Diseases (NIAID); Merlin L Robb, Walter Reed Army Institute of Research; Lawrence Corey, Rollins School of Public Health; Kathleen M Neuzil, University of Maryland School of Medicine; Dean Follmann, National Institute of Allergy and Infectious Diseases (NIAID); Corey Hoffman, United States Department of Health and Human Services; Ann R Falsey, University of Rochester; Magdalena Sobieszczyk, Columbia University Irving Medical Center; Richard A Koup, National Institute of Allergy and Infectious Diseases (NIAID); Rubern O Donis, United States Department of Health and Human Services; Peter B Gilbert, Fred Hutchinson Cancer Research Center
• Language: English
• Date: 2023-12-01
• Publisher: pringer Nature
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2023
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/s41541-023-00630-0
• Title of Journal or Parent Work: npj Vaccines
• Volume: 8
• Issue: 1
• Start Page: 36
• End Page: 36
• Keywords: AZD1222 (ChAdOx1 nCoV-19)
• Research Categories: Health Sciences, Public Health; Health Sciences, Pathology

Abstract

In the phase 3 trial of the AZD1222 (ChAdOx1 nCoV-19) vaccine conducted in the U.S., Chile, and Peru, anti-spike binding IgG concentration (spike IgG) and pseudovirus 50% neutralizing antibody titer (nAb ID50) measured four weeks after two doses were assessed as correlates of risk and protection against PCR-confirmed symptomatic SARS-CoV-2 infection (COVID-19). These analyses of SARS-CoV-2 negative participants were based on case-cohort sampling of vaccine recipients (33 COVID-19 cases by 4 months post dose two, 463 non-cases). The adjusted hazard ratio of COVID-19 was 0.32 (95% CI: 0.14, 0.76) per 10-fold increase in spike IgG concentration and 0.28 (0.10, 0.77) per 10-fold increase in nAb ID50 titer. At nAb ID50 below the limit of detection (< 2.612 IU50/ml), 10, 100, and 270 IU50/ml, vaccine efficacy was −5.8% (−651%, 75.6%), 64.9% (56.4%, 86.9%), 90.0% (55.8%, 97.6%) and 94.2% (69.4%, 99.1%). These findings provide further evidence towards defining an immune marker correlate of protection to help guide regulatory/approval decisions for COVID-19 vaccines.