Immune Correlates Analysis of the ENSEMBLE Single Ad26.COV2.S Dose Vaccine Efficacy Clinical Trial

• Type of Material: Article
• Authors: Youyi Fong, Fred Hutchinson Cancer Center; Adrian B. McDermott, National Institutes of Health; David Benkeser, Emory University; Sanne Roels, Janssen Pharmaceutica NV; Daniel J. Stieh, Janssen Vaccines and Prevention; An Vandebosch, Janssen Pharmaceutica NV; Mathieu Le Gars, Janssen Vaccines and Prevention; Griet A. Van Roey, Janssen Vaccines and Prevention; 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; Obrimpong Amoa-Awua, National Institutes of Health; Manjula Basappa, National Institutes of Health; Britta Flach, National Institutes of Health; Bob C. Lin, National Institutes of Health; Christopher Moore, National Institutes of Health; Mursal Naisan, National Institutes of Health; Muhammed Naqvi, National Institutes of Health; Sandeep Narpala, National Institutes of Health; Sarah O'Connell, National Institutes of Health; Allen Mueller, National Institutes of Health; Leo Serebryannyy, National Institutes of Health; Mike Castro, National Institutes of Health; Jennifer Wang, National Institutes of Health; Christos J. Petropoulos, LabCorp-Monogram Biosciences; Alex Luedtke, University of Washington; Ollivier Hyrien, Fred Hutchinson Cancer Center; Yiwen Lu, Fred Hutchinson Cancer Center; Chenchen Yu, Fred Hutchinson Cancer Center; Bhavesh Borate, Fred Hutchinson Cancer Center; Lars W.P. van der Laan, University of Washington; Nima S. Hejazi, Weill Cornell Medicine; Avi Kenny, University of Washington; Marco Carone, University of Washington; Daniel N. Wolfe, Biomedical Advanced Research and Development Authority; Jerald Sadoff, Janssen Vaccines and Prevention; Glenda E. Gray, University of the Witwatersrand; Beatriz Grinsztejn, Evandro Chagas National Institute of Infectious Diseases-Fundação Oswaldo Cruz; Paul A. Goepfert, University of Alabama, Birmingham; Susan J. Little, University of California, San Diego; Leonardo Paiva de Sousa, Evandro Chagas National Institute of Infectious Diseases-Fundação Oswaldo Cruz; Rebone Maboa, Ndlovu Elandsdoorn Site; April K. Randhawa, Fred Hutchinson Cancer Center; Michele P. Andrasik, Fred Hutchinson Cancer Center; Jenny Hendriks, Janssen Vaccines and Prevention; Carla Truyers, Janssen Pharmaceutica NV; Frank Struyf, Janssen Pharmaceutica NV; Hanneke Schuitemaker, Janssen Vaccines and Prevention; Macaya Douoguih, Janssen Vaccines and Prevention; James G. Kublin, Fred Hutchinson Cancer Center; Lawrence Corey, University of Washington; Kathleen M. Neuzil, University of Maryland, Baltimore; Lindsay N. Carpp, Fred Hutchinson Cancer Center; Dean Follmann, National Institutes of Health; Peter B. Gilbert, University of Washington; Richard A. Koup, National Institutes of Health; Ruben O. Donis, Biomedical Advanced Research and Development Authority
• Language: English
• Date: 2022-11-10
• Publisher: Springer Nature
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2022, The Author(s), under exclusive licence to Springer Nature Limited
• Final Published Version (URL): https://doi.org/10.1038/s41564-022-01262-1
• Title of Journal or Parent Work: Nature Microbiology
• Volume: 7
• Issue: 12
• Start Page: 1996
• End Page: 2010
• Grant/Funding Information: This work was partially funded by the Office of the Assistant Secretary for Preparedness and Response, Biomedical Advanced Research and Development Authority, under Government Contract Nos. HHSO100201700018C with Janssen and 75A50122C00008 with Labcorp – Monogram Biosciences; by the National Institutes of Health, National Institute of Allergy and Infectious Diseases (NIAID) under Public Health Service Grants UM1 AI068635 (HVTN SDMC) (PBG), UM1 AI068614 (HVTN LOC) (LC), and R37AI054165 (PBG); and by the Intramural Research Program of the NIAID Scientific Computing Infrastructure at Fred Hutch, under ORIP grant S10OD028685. This work was also supported by Janssen Research and Development, an affiliate of Janssen Vaccines and Prevention and part of the Janssen pharmaceutical companies of Johnson & Johnson.
• Keywords: immune correlates of disease acquisition; Ad26.COV2.S vaccine; clinical trial
• Research Categories: Health Sciences, Epidemiology; Health Sciences, Immunology

Abstract

Measuring immune correlates of disease acquisition and protection in the context of a clinical trial is a prerequisite for improved vaccine design. We analyzed binding and neutralizing antibody measurements four weeks post-vaccination as correlates of risk of moderate to severe-critical COVID-19 through 83 days post-vaccination in the phase III, double-blind placebo-controlled phase of ENSEMBLE, an international, randomized efficacy trial of a single dose of Ad26.COV2.S. We also evaluated correlates of protection in the trial cohort. Of the three antibody immune markers we measured, we found most support for 50% inhibitory dilution (ID50) neutralizing antibody titer as a correlate of risk and of protection. The outcome hazard ratio was 0.49 (95% confidence interval 0.29, 0.81; p=0.006) per 10-fold increase in ID50; vaccine efficacy was 60% (43, 72%) at nonquantifiable ID50 (< 2.7 IU50/ml) and increased to 89% (78, 96%) at ID50 = 96.3 IU50/ml. Comparison of the vaccine efficacy by ID50 titer curves for ENSEMBLE-US, the COVE trial of the mRNA-1273 vaccine, and the COV002-UK trial of the AZD1222 vaccine supported that ID50 titer is a correlate of protection across trials and vaccine types.