Omicron COVID-19 Immune Correlates Analysis of a Third Dose of mRNA-1273 in the COVE Trial
Author:
Zhang Bo, Fong Youyi, Fintzi Jonathan, Chu Eric, Janes Holly E., Carpp Lindsay N.ORCID, Kenny Avi, Carone Marco, Benkeser DavidORCID, van der Laan Lars W. P., Deng Weiping, Zhou Honghong, Wang Xiaowei, Lu Yiwen, Yu Chenchen, Borate Bhavesh, Houchens Christopher R., Martins Karen, Jayashankar Lakshmi, Huynh Chuong, Fichtenbaum Carl J., Kalams Spyros, Gay Cynthia L., Andrasik Michele P., Kublin James G., Corey Lawrence, Neuzil Kathleen M., Priddy Frances, Das Rituparna, Girard Bethany, El Sahly Hana M., Baden Lindsey R., Donis Ruben O., Koup Richard A., Gilbert Peter B., Follmann Dean, , ,
Abstract
AbstractIn the coronavirus efficacy (COVE) phase 3 efficacy trial of the mRNA-1273 vaccine, IgG binding antibody (bAb) concentration against Spike (BA.1 strain) and neutralizing antibody (nAb) titer against Spike (BA.1 strain) pseudovirus were assessed as correlates of risk of Omicron COVID-19 and as correlates of relative boost efficacy in per-protocol recipients of a third (booster) dose. Markers were measured on the day of the boost (BD1) and 28 days later (BD29). For SARS-CoV-2 naive individuals, BD29 Spike IgG-BA.1 strain bAbs and BD29 BA.1-strain nAbs inversely correlated with Omicron COVID-19: hazard ratio (HR) per 10-fold marker increase [95% confidence interval (CI)] = 0.16 (0.03, 0.79); P=0.024 and 0.31 (0.10, 0.96); P = 0.042, respectively. These markers also inversely correlated with Omicron COVID-19 in non-naive individuals: HR = 0.15 (0.04, 0.63); P = 0.009 and 0.28 (0.07, 1.08); P = 0.06, trend. Fold-rise in markers from BD1 to BD29 had similarly strong inverse correlations. For SARS-CoV-2 naive individuals, overall booster relative (three-dose vs two-dose) efficacy was 46% (95% CI: 20%, 64%) and correlated with BA.1 strain nAb titer at exposure. At 56, 251, and 891 arbitrary units (AU)/ml (10th, 50th, and 90thpercentile), the booster relative efficacies were −8% (95% CI: −126%, 48%), 50% (25%, 67%), and 74% (49%, 87%), respectively. Similar relationships were observed for Spike IgG-BA.1 strain bAbs and for the markers measured at BD29. The performance of bAb and nAb markers as correlates of protection against Omicron COVID-19 supports their continued use as surrogate endpoints for mRNA vaccination against Omicron COVID-19.
Publisher
Cold Spring Harbor Laboratory
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