Higher antibody level correlates with greater vaccine protection against COVID-19

By measuring antibodies against the SARS-CoV-2 spike protein in participants in a phase 3 trial of the Moderna COVID-19 vaccine, researchers found that the higher the antibody level, the greater the vaccine protection against COVID-19.

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 a disease such as COVID-19.

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 and colleagues assessed whether the same SARS-CoV-2 antibody markers were correlates of vaccine protection in a phase 3 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. 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. Antibody levels that predict mRNA vaccine efficacy can therefore be used to guide vaccine regimen modifications, the authors say.