Eagerly anticipated new research pinpoints antibodies scientists can test for to see if a COVID-19 vaccine is effective. These “correlates of protection” could speed the development of new vaccines or boosters without requiring the enormous clinical trials used to create the first COVID-19 vaccines.
Instead, researchers could vaccinate people with a new vaccine or booster, measure their antibodies over the course of several months, and know if it worked.
This is “the Holy Grail” in terms of vaccines, and one that hasn’t yet been set for the virus that causes COVID-19, said Peter Gilbert, co-author of the study posted Tuesday to medRxiv, a preprint site where scientific articles can be published prior to being accepted by peer-reviewed journals.
“The hope is that the Food and Drug Administration will see these data and use them as a provisional approval mechanism,” he said.
Gilbert is a biostatistician at the Fred Hutchinson Cancer Research Center in Seattle, who also leads the statistical center for the federal government’s COVID-19 Prevention Network.
While the study has not been subject to the strict peer-review required by standard scientific journals, such preprints have become common during the COVID-19 pandemic. Gilbert and his co-authors are highly regarded researchers, who have previously published on the topic of correlates of protection and have submitted the paper to a standard journal.
“This is a well done and important piece of collaborative work,” said Dr. Jesse Goodman, a professor of medicine and infectious diseases at Georgetown University, who was not affiliated with the research.
Such correlates have long been used to help create vaccines for other diseases, such as influenza.
“Such measurements should help speed evaluation, including by regulators, of vaccines being used in new populations and/or being made with variants.”
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Measuring ‘soldiers on the field’
The researchers with the Coronavirus Efficacy (COVE) study measured levels of two markers of antibodies in the blood of study participants to see if they correlated with COVID-19 risk.
The study took place from July to October 2020 and included 30,415 participants. Half received two doses of the Moderna vaccine, half received a placebo. Of those, 1,051 recipients of the vaccine had their antibodies measured.
Two types of markers were measured: neutralizing antibodies and binding antibodies. Both types have been used as correlates for protection for vaccines against other viral diseases.
The markers for neutralization measure how strongly antibodies block the virus from infecting cells. The markers for binding antibodies measure how many antibodies latch on to the spike protein.
“You could say it measures how many soldiers see the virus and get onto the battlefield,” Gilbert said.
Participants’ blood was tested for levels of the markers twice, once after their second shot of Moderna’s COVID-19 vaccine and again four weeks later.
The higher the amount of antibodies participants had the lower their chance of getting COVID-19. That was true for all antibody markers at both time points.
The effect lasted through four months after the second dose of the vaccine. It may last longer but the study is still ongoing. Future research will look at whether lower antibody levels correspond to more severe cases of COVID-19 and if there’s any correlation between age or health issues.
It’s important to remember that the antibody levels measured may not represent all that’s protecting people against the virus, Goodman said.
“Antibody levels may wane but other aspects of the immune system, not reported on in this study, such as T cells and memory B cells, may potentially still help provide substantial protection against disease, and particularly against severe outcomes,” he said.
Because of that, it’s still not possible to say waning antibodies are truly predictive of risk. Studies evaluating actual clinical protection and how well it correlates with the antibody levels are still needed, he said.
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Strong connection between antibodies, protection
Similar data has recently been published by Oxford University in England about the AstraZeneca vaccine and in Israel about the Pfizer vaccine. In both studies, higher antibody levels corresponded with lower rates of disease.
While they used different tests to measure the levels, they are evidence of a strong connection between antibodies and protection.
The antibody levels the researchers looked at don’t mean individuals can go out and get their blood drawn to see if they’ve mounted an effective antibody response to the virus, Gilbert said.
“I don’t think anybody is talking about individuals going into a clinic, finding out their antibodies are low and getting revaccinated. That’s not really the goal of this research,” he said. “It’s to provide a way to approve new vaccines quickly.”
One of the tests used by the researchers is not readily available at the average medical laboratory, said Alan Wu, a professor of laboratory medicine at the University of California, San Francisco, and chief of the clinical chemistry and toxicology laboratories at Zuckerberg San Francisco General Hospital.
The test also doesn’t measure all that’s going on in someone’s immune system.
“How do you interpret results, as neutralizing antibodies are only half the picture? We also have T-cell immunity,” said Wu.
