After people have been vaccinated against COVID-19, the levels of infection-blocking antibodies in their blood are a strong indicator of how much protection they’ve gained against the disease, according to a modelling study¹. The research showed that the presence of even small quantities of these potent ‘neutralizing antibodies’ indicates that a vaccine is effective at protecting against COVID-19.

The study is the best attempt yet to define features of the immune response that can act as a proxy for protection against COVID-19, known as a ‘correlate of protection’, says Daniel Altmann, an immunologist at Imperial College London. “Finding the correlate of protection has really been a holy grail for this disease, as for others. It’s surprisingly hard to do.”

If researchers have a well-defined correlate of protection, they can predict from early trial data how effective a vaccine will be, says James Triccas, a medical microbiologist at the University of Sydney in Australia and a co-author of the study. This “alleviates the need to do larger, more expensive and time-consuming phase III trials”.

Triccas and his colleagues examined neutralizing-antibody data from trials of seven widely used vaccines. The team found a strong link between participants’ antibody levels recorded in early-stage trials and vaccine-efficacy results from late-stage trials. The researchers estimate that a vaccine has an efficacy of 50% even if it induces antibody levels 80% lower than those found, on average, in a person who has recovered from COVID-19.

Vaccines that generated the strongest neutralizing-antibody responses, such as the mRNA-based vaccines made by Moderna and Pfizer–BioNTech, were the most protective. Vaccines that induced a weaker response, which included the Oxford–AstraZeneca jab, provided lower levels of protection.

The researchers predict that because antibody levels wane over time, booster shots might be needed in about a year, but protection against severe disease could last many years even without them.

The findings help to explain why, despite studies showing that some variants of the SARS-CoV-2 coronavirus reduce the ability of neutralizing antibodies to block infection, most people who have been vaccinated, even with just one dose, don’t fare too badly if infected with those variants, says Altmann. “Even low antibody levels, lower than we thought, will probably see you through.”

More studies are needed to pin down which cells or molecules determine the level of protection, says Dan Barouch, director of the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center in Boston, Massachusetts. This could differ by vaccine technology, he says.