1. Omicron COVID-19 immune correlates analysis of a third dose of mRNA-1273 in the COVE trial.
- Author
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Zhang B, Fong Y, Fintzi J, Chu E, Janes HE, Kenny A, Carone M, Benkeser D, van der Laan LWP, Deng W, Zhou H, Wang X, Lu Y, Yu C, Borate B, Chen H, Reeder I, Carpp LN, Houchens CR, Martins K, Jayashankar L, Huynh C, Fichtenbaum CJ, Kalams S, Gay CL, Andrasik MP, Kublin JG, Corey L, Neuzil KM, Priddy F, Das R, Girard B, El Sahly HM, Baden LR, Jones T, Donis RO, Koup RA, Gilbert PB, and Follmann D
- Subjects
- Humans, COVID-19 Vaccines immunology, COVID-19 Vaccines administration & dosage, Female, Male, Adult, Vaccine Efficacy, COVID-19 immunology, COVID-19 virology, COVID-19 prevention & control, SARS-CoV-2 immunology, Antibodies, Neutralizing immunology, Antibodies, Viral immunology, Antibodies, Viral blood, Spike Glycoprotein, Coronavirus immunology, Immunization, Secondary, 2019-nCoV Vaccine mRNA-1273 administration & dosage, 2019-nCoV Vaccine mRNA-1273 immunology
- 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., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)
- Published
- 2024
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