Immune Correlates Analysis of the mRNA-1273 COVID-19 Vaccine Efficacy Trial

作者：Peter B. Gilbert, David C. Montefiori, Adrian B. McDermott, Youyi Fong, David Benkeser, Weiping Deng, Honghong Zhou, Christopher R. Houchens, Karen Martins, Lakshmi Jayashankar, Flora Castellino, Britta Flach, Bob C. Lin, Sarah O’Connell, Charlene McDanal, Amanda Eaton, Marcella Sarzotti‐Kelsoe, Yiwen Lu, Chenchen Yu, Bhavesh Borate, Lars W. P. van der Laan, Nima S. Hejazi, Chuong Huynh, Jacqueline M. Miller, Hana M. El Sahly, Lindsey R. Baden, Mira Baron, Luis de la Cruz‐Merino, Cynthia L. Gay, Spyros A. Kalams, Colleen F. Kelley, Mark E Kutner, Michele P. Andrasik, James G. Kublin, Lawrence Corey, Kathleen M. Neuzil, Lindsay N. Carpp, Rolando Pajón, Dean Follmann, Rubén O. Donis, Richard A. Koup · 发表于：medRxiv · 年份：2021 · DOI：10.1101/2021.08.09.21261290 · 被引用次数：139 · 研究领域：SARS-CoV-2 and COVID-19 Research、COVID-19 Clinical Research Studies、vaccines and immunoinformatics approaches

BACKGROUND: In the Coronavirus Efficacy (COVE) trial, estimated mRNA-1273 vaccine efficacy against coronavirus disease-19 (COVID-19) was 94%. SARS-CoV-2 antibody measurements were assessed as correlates of COVID-19 risk and as correlates of protection. METHODS: Through case-cohort sampling, participants were selected for measurement of four serum antibody markers at Day 1 (first dose), Day 29 (second dose), and Day 57: IgG binding antibodies (bAbs) to Spike, bAbs to Spike receptor-binding domain (RBD), and 50% and 80% inhibitory dilution pseudovirus neutralizing antibody titers calibrated to the WHO International Standard (cID50 and cID80). Participants with no evidence of previous SARS-CoV-2 infection were included. Cox regression assessed in vaccine recipients the association of each Day 29 or 57 serologic marker with COVID-19 through 126 or 100 days of follow-up, respectively, adjusting for risk factors. RESULTS: Day 57 Spike IgG, RBD IgG, cID50, and cID80 neutralization levels were each inversely correlated with risk of COVID-19: hazard ratios 0.66 (95% CI 0.50, 0.88; p=0.005); 0.57 (0.40, 0.82; p=0.002); 0.42 (0.27, 0.65; p<0.001); 0.35 (0.20, 0.61; p<0.001) per 10-fold increase in marker level, respectively, multiplicity adjusted P-values 0.003-0.010. Results were similar for Day 29 markers (multiplicity adjusted P-values <0.001-0.003). For vaccine recipients with Day 57 reciprocal cID50 neutralization titers that were undetectable (<2.42), 100, or 1000, respectively, c...