1. Omicron COVID-19 immune correlates analysis of a third dose of mRNA-1273 in the COVE trial
- Author
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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, and USG/CoVPN Biostatistics Team
- Subjects
Science - 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.
- Published
- 2024
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