Immune Correlates Analysis of the mRNA-1273 COVID-19 Vaccine Efficacy Trial
Author:
Gilbert Peter B., Montefiori David C., McDermott Adrian, Fong Youyi, Benkeser DavidORCID, Deng Weiping, Zhou Honghong, Houchens Christopher R., Martins Karen, Jayashankar Lakshmi, Castellino Flora, Flach Britta, Lin Bob C., O’Connell Sarah, McDanal Charlene, Eaton Amanda, Sarzotti-Kelsoe Marcella, Lu Yiwen, Yu Chenchen, Borate Bhavesh, van der Laan Lars W. P., Hejazi Nima, Huynh Chuong, Miller Jacqueline, El Sahly Hana M.ORCID, Baden Lindsey R., Baron Mira, De La Cruz Luis, Gay Cynthia, Kalams Spyros, Kelley Colleen F., Kutner Mark, Andrasik Michele P., Kublin James G., Corey Lawrence, Neuzil Kathleen M., Carpp Lindsay N.ORCID, Pajon Rolando, Follmann Dean, Donis Ruben O., Koup Richard A.
Abstract
AbstractBackgroundIn 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.MethodsThrough 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.ResultsDay 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, cumulative incidence of COVID-19 through 100 days post Day 57 was 0.030 (0.010, 0.093), 0.0056 (0.0039, 0.0080), and 0.0023 (0.0013, 0.0036). For vaccine recipients at these titer levels, respectively, vaccine efficacy was 50.8% (−51.2, 83.0%), 90.7% (86.7, 93.6%), and 96.1% (94.0, 97.8%). Causal mediation analysis estimated that the proportion of vaccine efficacy mediated through Day 29 cID50 titer was 68.5% (58.5, 78.4%).ConclusionsBinding and neutralizing antibodies correlated with COVID-19 risk and vaccine efficacy and likely have utility in predicting mRNA-1273 vaccine efficacy against COVID-19.Trial registration numberCOVE ClinicalTrials.gov number, NCT04470427
Publisher
Cold Spring Harbor Laboratory
Reference48 articles.
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