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

Our take —

This study examined a sub-cohort of participants in the phase three Coronavirus Efficacy vaccine (COVE) trial to identify antibody immune markers as correlates of protection against COVID-19 in individuals who received two doses of Moderna’s mRNA-1273 vaccine. All of the immune markers assessed showed an inverse correlation with risk of COVID-19 disease and were positively correlated with vaccine efficacy providing possible immune marker endpoints for future vaccine trials.

Study design

Randomized Controlled Trial

Study population and setting

This study examined a sub-cohort of participants in the phase 3 Coronavirus Efficacy (COVE) clinical trial of the mRNA-1273 vaccine(Moderna) to assess neutralizing and binding antibodies as correlates of protection against COVID-19 disease. Antibody markers including IgG against the spike protein and receptor binding domain (RBD) proteins and ID50 and ID80 inhibitory dilution titers were assessed as possible correlates. The sub-cohort included 1010 vaccine and 137 placebo recipients. 34% of participants were age 65 or older, and 40% were considered to be at risk for severe COVID-19 illness. Correlates were measured on days 29 and 57 after the second vaccine dose

Summary of Main Findings

Nearly all vaccine recipients had detectable IgG antibody responses by day 29 and detectable responses for all four immune markers by day 57. Spike IgG and RBD IgG were tightly correlated with each other, as were the ID50 and ID80 inhibitory dilution titers. Additionally, each of the binding antibody markers were correlated with each of the neutralization markers at each time point. Among 1,010 vaccinated participants, 46 experienced COVID-19 by day 29 and 36 more developed COVID-19 by day 57. Vaccine recipients who contracted COVID-19 had lower levels of markers compared to vaccine recipient non-cases. As the antibody marker level increased, the risk of COVID-19 in vaccine recipients decreased; there were zero COVID-19 endpoints at ID50 titers above 1000 IU50/ml. That said, there was substantial overlap between markers in vaccinated individuals with COVID-19 and without, precluding any measurement at individual levels that could lead to specific recommendations about protection or the need for boosting.

Study Strengths

This study cohort was diverse, including 54% of participants from communities of color, and included many participants at risk of severe COVID-19 disease. The COVE study will continue follow up with participants for two years, allowing longer term data to be collected.

Limitations

This study has several limitations. First of all, the results could simply represent statistical correlates of protection rather than mechanistic correlates. The study did not assess immune correlates against severe COVID-19 outcomes, although preventing this outcome is the primary goal of vaccines. The study also did not assess the role of T cell immunity on prevention of infection. Almost all COVID-19 cases in this study resulted from COVID-19 strains with spike protein similar to the sequence found in the mRNA-1273 vaccine. Therefore, the data here do not address immune marker correlates relative to variants of concern. This study was also performed before booster doses of mRNA-1273 were approved, so the effects of a third dose were unable to be analyzed.

Value added

This study defined immune marker correlates of protection against COVID-19 in individuals who received two doses of Moderna’s mRNA-1273 vaccine, providing possible immune marker endpoints for future vaccine trials.

This review was posted on: 5 January 2022