Immune correlates analysis of the mRNA-1273 COVID-19 vaccine efficacy clinical trial

TLDR

In the COVE phase 3 trial, neutralizing and binding antibody levels were measured at the second dose and four weeks later, expressed in WHO international units, to evaluate their role as correlates of COVID‑19 risk and vaccine protection. Higher antibody titers were inversely linked to COVID‑19 risk and directly to vaccine efficacy, with 50% neutralization titers of 10, 100, and 1000 predicting 78 %, 91 %, and 96 % efficacy, respectively, thereby defining correlates that can inform vaccine approvals.

Abstract

In the coronavirus efficacy (COVE) phase 3 clinical trial, vaccine recipients were assessed for neutralizing and binding antibodies as correlates of risk for COVID-19 disease and as correlates of protection. These immune markers were measured at the time of second vaccination and 4 weeks later, with values reported in standardized World Health Organization international units. All markers were inversely associated with COVID-19 risk and directly associated with vaccine efficacy. Vaccine recipients with postvaccination 50% neutralization titers 10, 100, and 1000 had estimated vaccine efficacies of 78% (95% confidence interval, 54 to 89%), 91% (87 to 94%), and 96% (94 to 98%), respectively. These results help define immune marker correlates of protection and may guide approval decisions for messenger RNA (mRNA) COVID-19 vaccines and other COVID-19 vaccines.