Vaccines against SARS-CoV-2, the virus that causes COVID-19, were produced, tested, and approved in record time. The clinical trials assessing the safety and effectiveness of these vaccines required tens of thousands of volunteers.

With the continued emergence of new SARS-CoV-2 variants, and the possibility that COVID-19 vaccines might need to be modified in response, researchers are seeking ways to streamline vaccine trials. Markers of immune response that could predict the protection conferred by vaccination would allow for clinical trials that use fewer volunteers.

Toward this end, researchers led by Dr. Peter Gilbert from the Fred Hutchinson Cancer Research Center measured antibodies in the blood of more than 1,000 people who had received the two-dose Moderna COVID-19 vaccine. The team measured binding antibodies, which bind viruses to tag them for destruction, and neutralizing antibodies, which stop viruses from infecting cells by blocking the parts they need to enter.

The researchers looked for associations between levels of antibodies post-vaccination and the risk of symptomatic COVID-19 infections. The study was funded in part by NIH’s National Institute of Allergy and Infectious Diseases (NIAID) and Office of the Director (OD). Results were published on November 23, 2021, in Science.

Antibodies were measured in blood samples taken 4 weeks after the first and second vaccine doses. Levels of both binding and neutralizing antibodies were lower in people who later developed COVID-19 than in people who didn’t get sick. The protection conferred by the vaccine increased as levels of these antibodies increased.

For example, for people with no detectible neutralizing antibodies, the vaccine was only 51% effective. For people with the highest levels, it was 98% effective. Based on any of the measures, the risk of COVID-19 was about 10 times lower for people with the top 10% of antibody levels compared to those with the lowest levels.

Binding and neutralizing antibodies had similar associations with vaccine effectiveness. The team also looked at blood samples from two other studies: a clinical trial of the Oxford/AstraZeneca vaccine in the U.K. and non-human primate studies of the Moderna vaccine. They saw similar correlations between levels of neutralizing antibodies and vaccine effectiveness in both studies.

These antibody tests, or assays, have the potential to allow smaller and quicker trials. However, Gilbert points out, “It remains crucial that we also follow up any provisional decisions based on such assays with direct verification.”

It’s not yet known if these short-term antibody measures correlate with long-term protection. Other parts of the immune response help protect against viruses as well. The study also did not look at antibodies after a booster dose. The participants will be followed for a total of two years to gain more insights.

This research brief was originally published by theNational Institutes of Health on December 7, 2021.