COVID-19 vaccine boosters are likely to be a hot topic of conversation around many Thanksgiving gatherings this week. The idea of a booster is, in part, to increase the number of circulating antibodies being made against SARS-CoV-2. But, it has remained unknown how correlated the level of antibodies is to the level of protection against infection. Now, by measuring antibodies against the SARS-CoV-2 spike protein in participants in a Phase III trial of the Moderna COVID-19 vaccine, researchers found that the higher the antibody level, the greater the vaccine protection against COVID-19.

This work is published in Science, in the paper, “Immune correlates analysis of the mRNA-1273 COVID-19 vaccine efficacy clinical trial.”

The results help define “correlates of protection”—or molecular biomarkers to measure how much immunity is needed to fight infection—and may guide approval decisions for mRNA COVID-19 vaccines and other COVID-19 vaccines. Immune marker correlates of protection can be used to reliably predict the level of vaccine efficacy against infection such as SARS-CoV-2. As such, they are highly sought in vaccine research; identification and validation of a correlate of protection would expedite the clinical evaluation and regulatory approval process for existing vaccines for new populations, for vaccine regimen modifications, and for new vaccines. Neutralizing antibodies (nAbs) or binding antibodies (bAbs) have been established as a correlate of protection for vaccines against many viral diseases. The hypothesis that antibodies, whether elicited by infection or by spike protein-based vaccines, are a correlate of protection against COVID-19 is supported by diverse lines of evidence.

Here, following previous assessments by other groups in non-human primates in which each of several antibody markers correlated with protection against SARS-CoV-2 replication after challenge in vaccinated rhesus macaques, Peter Gilbert, PhD, professor in the biostatistics, bioinformatics, and epidemiology program and the vaccine and infectious disease division at the Fred Hutch, and colleagues, assessed whether the same SARS-CoV-2 antibody markers were correlates of vaccine protection in a Phase III trial of the mRNA-1273 COVID-19 vaccine.

By measuring binding and neutralizing antibodies against the viral spike protein, they found that the higher the antibody level, the greater the protection afforded by the mRNA vaccine.

The team assessed anti-spike, anti-receptor binding domain IgG, and neutralizing antibodies in vaccine recipients as correlates of risk for COVID-19 and as correlates of protection. The immune markers were measured at the second vaccination and four weeks later.

Based on any of the antibody markers, estimated COVID-19 risk was about 10 times lower for vaccine recipients with antibodies in the top 10% of values compared to those with negative/undetectable values.

All markers, the authors wrote, were inversely associated with COVID-19 risk and directly associated with vaccine efficacy. Vaccine recipients with post-vaccination 50% neutralization titers 10, 100, and 1000 had estimated vaccine efficacy of 78%, 91%, and 96%, respectively.

These results, the authors noted, help define immune marker correlates of protection with applications including to support provisional or traditional approval decisions for mRNA COVID-19 vaccines and potentially for other COVID-19 vaccines.