New evidence indicates that antibodies are a reliable indicator of vaccine protection

When Dr.Anthony Fauci recently spoke at a White House briefing on the need for COVID-19 booster vaccines, buried in his slideshow of charts and data points was a little-noticed scientific article that offers evidence of a reliable way to predict how much protection a COVID-19 vaccine offers.

The study appeared on a preprint server earlier this month without much fanfare, but many people interested in the future of COVID-19 vaccines were eagerly awaiting the results.

The researchers were looking for markers in the blood of vaccinated patients that would indicate protection against COVID-19, so-called “correlates of immunity.” What the team of scientists have found are neutralizing antibodies – proteins made by the immune system that are known to disarm the coronavirus.

As Fauci explained, the paper showed that higher levels of these antibodies are associated with higher levels of vaccine efficacy. The results suggest that giving people a booster vaccine, which has been shown to increase antibody levels, would go a long way in protecting them against the coronavirus, including some of the newer and more dangerous variants.

Although more studies are needed to confirm the results, finding out that these markers correlate with immune protection has implications for future COVID-19 vaccine research. That means researchers can now measure whether a new COVID-19 vaccine might work – without necessarily having to repeat large-scale efficacy studies.

“This could be used as the basis for the authorization and approval of candidate vaccines without needing to do these trials with 40,000 people which take a lot of time and a lot of money to complete,” says Peter Gilbert, biostatistician at Fred Hutchinson Cancer Research Center. , the lead author of the new study.

Why we need immunity correlates

To understand if there is a protective level of neutralizing antibodies, a team of researchers from academia, industry and government conducted new research on the blood of people who participated in the large Moderna vaccine trial. This older trial, involving 30,000 volunteers, was the basis for the Food and Drug Administration which granted Moderna emergency use authorization for its COVID-19 vaccine.

This new research found 46 people in the Moderna study who had been vaccinated but then became ill with COVID-19 and compared their levels of neutralizing antibodies with the levels found in a sample of 1,000 people who were vaccinated for the test and never got sick.

“[The antibody levels] were consistently lower in vaccinated people who became a case of COVID compared to people who remained free from COVID, ”Gilbert said.

The results show that antibody levels can be predictive of immunity, which should help develop and test new vaccines at a much faster rate. It’s even possible that manufacturers of COVID-19 vaccines don’t need to conduct trials with large numbers of people to see how many get sick after being vaccinated. Instead, researchers could simply draw blood and look for antibody levels that correlate with protection.

“So maybe they would only need to study a few hundred people instead of tens of thousands if they wanted to show that a vaccine worked,” says Gilbert.

No magic number yet

The four markers of immunity identified in the document should indicate how well a COVID-19 vaccine works overall, but the blood test cannot inform an individual person of their level of protection.

It would be great if the antibody level were a specific number, but it isn’t, says Emory University biostatistician David Benkeser, another study author.

“Unfortunately, the story is a bit more subtle than that,” he says. “We really see it as a continuum. Some antibodies [are] Well. More is better. “

In fact, it’s pretty clear that antibodies alone don’t explain why some people are protected, and other parts of the immune system also play an important role in fighting the coronavirus, including T cells.

“Two percent of those vaccinated had very, very low levels. Antibody levels below this lower limit of detection,” says Christopher Houchens, biomedical researcher at the Biomedical Advanced Research and Development Authority, another author of the study. . “However, about 50% of those individuals in that 2% of the population were still protected and did not contract the symptomatic COVID-19 disease.”

More research needed to convince federal regulators

Researchers plan to do a similar analysis of the association between antibodies and vaccine-induced immunity in people who participated in the Johnson & Johnson and AstraZeneca COVID vaccine trials to see if the same pattern holds.

There are also plans to collect data in so-called challenge studies, where vaccinated people are deliberately infected with the coronavirus to see how well the vaccine protects them against infection or disease.

Ultimately, more studies will be needed to convince federal regulators that antibody levels alone may be sufficient evidence to support the authorization and approval of a future COVID-19 vaccine.

It is not a surprise.

“The science is not simple,” says Holly Janes, a biostatistician at the Fred Hutchinson Cancer Research Center who worked on the design of the antibody study. “It’s not neat and tidy. It’s important to look at things in different ways, in different kinds of studies, different kinds of analysis and different data sources, and that’s how we get the truth. . There is hardly ever a study that tells us everything we need to know. “

Copyright NPR 2021.