Comparing antibody assays as correlates of protection against COVID-19 in the COVE mRNA-1273 vaccine efficacy trial

• DOI: 10.1126/scitranslmed.ade9078
• Publication Date: 2023-04-19T13:58:18Z
• Authors: David Benkeser; David C. Montefiori; Adrian B. McDermott; Youyi Fong; Holly E. Janes; Weiping Deng; Honghong Zhou; Christopher R. Ho...; Karen Martins; Lakshmi Jayashankar; Flora Castellino; Britta Flach; Bob C. Lin; Sarah O’Connell; Charlene McDanal; Amanda Eaton; Marcella Sarzotti...; Yiwen Lu; Chenchen Yu; Bhavesh Borate; Lars W. P. van de...; Nima S. Hejazi; Avi Kenny; Marco Carone; Brian D. Williamson; Jennifer Garver; Erin Altonen; Thomas Rudge; Chuong Huynh; Jacqueline Miller; Hana M. El Sahly; Lindsey R. Baden; Sharon Frey; Elissa Malkin; Stephen A. Spector; Michele P. Andrasik; James G. Kublin; Lawrence Corey; Kathleen M. Neuzil; Lindsay N. Carpp; Rolando Pajon; Dean Follmann; Ruben O. Donis; Richard A. Koup; Peter B. Gilbert
• Keywords: 2019-20 coronavirus outbreak; Vaccine efficacy

The best assay or marker to define mRNA-1273 vaccine–induced antibodies as a correlate of protection (CoP) is unclear. In the COVE trial, participants received two doses COVID-19 vaccine placebo. We previously assessed IgG binding spike protein (spike IgG) receptor domain (RBD and pseudovirus neutralizing antibody 50 80% inhibitory dilution titer measured on day 29 57, correlates risk (CoRs) CoPs against symptomatic over 4 months after dose. Here, we new marker, live virus 50% microneutralization (LV-MN ), compared combined markers in multivariable analyses. LV-MN was an inverse CoR, with hazard ratio 0.39 (95% confidence interval, 0.19 0.83) at 0.51 0.25 1.04) 57 per 10-fold increase. analyses, neutralization titers anti-spike performed CoRs; combining did not improve correlates. Pseudovirus strongest independent model. Overall, these results supported assays CoRs CoPs, weaker this sample set. Day well which could accelerate immunogenicity immunobridging studies.