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Immune correlates analysis of the ENSEMBLE single Ad26.COV2.S dose vaccine efficacy clinical trial

2022; Nature Portfolio; Volume: 7; Issue: 12 Linguagem: Inglês

10.1038/s41564-022-01262-1

2058-5276

Youyi Fong, Adrian B. McDermott, David Benkeser, Sanne Roels, Daniel J. Stieh, An Vandebosch, Mathieu Le Gars, Griet A. Van Roey, Christopher R. Houchens, Karen Martins, Lakshmi Jayashankar, Flora Castellino, Obrimpong Amoa-Awua, Manjula Basappa, Britta Flach, Bob C. Lin, Christopher A. Moore, Mursal Naisan, Muhammed Naqvi, Sandeep Narpala, Sarah O’Connell, Allen Mueller, Leo Serebryannyy, Mike Castro, Jennifer Wang, Christos J. Petropoulos, Alex Luedtke, Ollivier Hyrien, Yiwen Lu, Chenchen Yu, Bhavesh Borate, Lars W. P. van der Laan, Nima S. Hejazi, Avi Kenny, Marco Carone, Daniel Wolfe, Jerald Sadoff, Glenda Gray, Beatriz Grinsztejn, Paul Goepfert, Susan J. Little, Leonardo Paiva de Sousa, Rebone Maboa, April Randhawa, Michele P. Andrasik, Jenny Hendriks, Carla Truyers, Frank Struyf, Hanneke Schuitemaker, Macaya Douoguih, James G. Kublin, Lawrence Corey, Kathleen M. Neuzil, Lindsay N. Carpp, Dean Follmann, Peter B. Gilbert, Richard A. Koup, Rubén O. Donis,

CAR-T cell therapy research

Measuring immune correlates of disease acquisition and protection in the context of a clinical trial is a prerequisite for improved vaccine design. We analysed binding and neutralizing antibody measurements 4 weeks post vaccination as correlates of risk of moderate to severe-critical COVID-19 through 83 d post vaccination in the phase 3, 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 titre 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 non-quantifiable ID50 (<2.7 IU50 ml−1) and increased to 89% (78%, 96%) at ID50 = 96.3 IU50 ml−1. Comparison of the vaccine efficacy by ID50 titre curves for ENSEMBLE-US, the COVE trial of the mRNA-1273 vaccine and the COV002-UK trial of the AZD1222 vaccine supported the ID50 titre as a correlate of protection across trials and vaccine types. Gold-standard evidence for correlates of protection is provided by analysis of a randomized phase 3 trial of Ad26.COV2.S for protection against moderate to severe-critical COVID-19 disease.