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When Dr. Anthony Faucic spoke recently at a White House briefing on the need for COVID-19 booster shots, buried in its slideshow of charts and data points, was a little-noted scientific paper providing evidence for a reliable way to predict how much protection a COVID-19 vaccine would provide. offers .
The study appeared on a preprint server earlier this month without much ado, but many interested in the future of COVID-19 vaccines had been eagerly awaiting the results.
The researchers were looking for markers in the blood of vaccinated patients that would indicate protection against COVID-19, which is known as “immunity correlates.” What the team of scientists discovered were 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 effectiveness. The findings suggest that giving humans a booster vaccine, which has been shown to increase antibody levels, would go a long way in protecting against the coronavirus, including some of its newer and more dangerous variants.
While more studies are needed to confirm the findings, the discovery that these markers correlate with immune protection has implications for future research on COVID-19 vaccines. It means researchers can now measure whether a new COVID-19 vaccine could work — without necessarily repeating large-scale efficacy studies.
“That could be used as a basis for authorization and approval of vaccine candidates without having to do these 40,000-person trials that are time-consuming and costly,” says Peter Gilbert a biostatistician at the Fred Hutchinson Cancer Research Center, the lead author of the new study.
Why do we need immunity correlates?
To understand whether there is a protective level of neutralizing antibodies, a team of researchers from academic institutions, industry and government undertook new research on the blood of people who took part in the large trial of the Moderna vaccine. That older trial, which involved 30,000 volunteers, was the basis for the Food and Drug Administration authorizing Moderna for emergency use for its COVID-19 vaccine.
This new research found 46 people in the Moderna study who were vaccinated but then became sick with COVID and their levels of neutralizing antibodies compared to the levels found in a sample of 1,000 people who were vaccinated during the trial and never got sick. .
“[The antibody levels] were always lower in the vaccinated people who became a COVID case compared to people who remained free of COVID,” says Gilbert.
The results show that antibody levels can be predictive of immunity, which should help develop and test new vaccines at a much faster pace. In fact, COVID-19 vaccine manufacturers may not 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 have to study a few hundred people instead of tens of thousands if they wanted to show that a vaccine worked,” Gilbert says.
Not a magic number yet
The four markers of immunity identified in the paper are supposed to indicate how well a COVID vaccine works in general, but the blood test cannot tell an individual about their level of protection.
It would be great if the antibody level was a specific number, but it isn’t, says Emory University biostatistician David Benkeser, another author on the study.
“Unfortunately, the story is a bit more subtle than that,” he says. “We really see this more as a continuum. Some antibodies [are] Good. 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 the individuals who were vaccinated had very, very low levels of antibodies that were below that lower limit of detection,” says Christopher Houchens, a biomedical researcher with the Biomedical Advanced Research and Development Authority, another author of the study. “However, about 50 percent of those individuals in that two percent of the population were still protected and did not develop symptomatic COVID-19 disease.”
More research needed to convince federal regulators
Researchers plan to conduct a similar analysis of the association between antibodies and vaccine-induced immunity in people enrolled 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 from infection or disease.
Ultimately, multiple studies will be needed to convince federal regulators that antibody levels alone can be sufficient evidence to support authorization and approval of a future COVID vaccine.
That’s no surprise.
“Science is not easy,” says Holly Janes, a biostatistician at the Fred Hutchinson Cancer Research Center who worked on designing the antibody study. “It’s not clean and tidy. Looking at things in different ways, in different kinds of studies, different kinds of analysis and different data sources is important, and that’s how we get to the truth. There is almost never one study that tells us everything we must know.”