To understand vaccine-induced immunity more fully, researchers are comparing antibody levels in people who received the Moderna vaccine but still got COVID-19 with levels in people who got the vaccine but didn't fall ill.

To understand vaccine-induced immunity more fully, researchers are comparing antibody levels in people who received the Moderna vaccine but still got COVID-19 with levels in people who got the vaccine but didn't fall ill. / AFP via Getty Images

It took many months and tens of thousands of volunteers to gather the data showing that the current crop of COVID-19 vaccines are safe and effective.

But what if new vaccines are needed to deal with dangerous variants of the coronavirus? Waiting months is not an attractive option.

So researchers are trying to come up with tests that can be performed using a blood sample that will determine not only whether a vaccine will work but also for how long.

One approach for determining these so-called correlates of protection is underway at the University of Oxford. Researchers there are deliberately exposing volunteers to the coronavirus. The volunteers are all healthy young adults who have previously gotten sick with COVID-19.

"The reason we're doing the study is that we expect to see some level of protection against reinfection," says Helen McShane, professor of vaccinology and chief investigator for the project. "The key question is, how much? And what kind of immune response correlates with that protection."

Here's how McShane and her colleagues are hoping to answer that question.

When you get infected with a virus, your immune system produces antibodies that target the virus and fight it off.

If you recover from the viral infection, then the antibodies did their job.

What the Oxford researchers want to learn is what level of antibodies is enough to provide protection against future infection.

"It may be not possible to reinfect with an antibody level above a certain amount," McShane says.

Measuring antibody levels is done with a blood test, and answering that question should be a significant help in coping with the COVID-19 pandemic.

"Because we can use that level, or that cutoff if you like, to say, 'OK, anyone who has that level of antibodies, either induced by natural infection or by vaccination, is protected,' " says Chris Houchens, division director for chemical, biological, radiological and nuclear countermeasures at the U.S. government's Biomedical Advanced Research and Development Authority.

Knowing that cutoff level, also called the cutoff titer, should be particularly useful for figuring out how long the protection afforded by a vaccine will last. If, for example, you have antibody titers above that threshold 18 months after being vaccinated, then you can expect the vaccine will still be working.

Houchens says the antibody cutoff becomes what's called a correlate of protection, that is the levels of antibodies in the blood that will indicate whether a new vaccine would protect someone without having to test it in tens of thousands of volunteers.

"We're going to want to be able to use the correlates of protection to conduct smaller studies that are going to involve the enrollment of patients rather than tens of thousands of patients," he says.

Houchens is involved in another effort to get at the antibody levels needed to achieve protection. Researchers are comparing antibody levels in people who received the Moderna vaccine but still got COVID-19 with levels in people who received the vaccine but didn't get sick.

Biostatistician Peter Gilbert from the Fred Hutchinson Cancer Research Center is leading the data analysis team for that effort.

The researchers look at the antibody levels of some 1,600 who received the Moderna COVID-19 vaccine as part of a large study that established the vaccine's efficacy. Three blood samples were analyzed.

"The sample that was drawn on the first date they got the vaccination, the sample that was drawn on the date they got the second vaccination, and then the sample that was drawn four weeks after the second vaccination," Gilbert says. By that last sample, an individual's antibodies should have reached a protective level. The question is — will the people who were vaccinated and still got sick have lower levels of antibodies than those who didn't get sick?

"Because the Moderna vaccine is so very effective, it's taken a very long time to collect enough from the vaccinated individuals who became infected," Houchens says.

But now they have, and Gilbert and his colleagues are assembling them in a database that they will run their analyses on.

"Then we'll be able to basically push the button — actually Moderna will push the button as a partnership and that will produce statistical reports containing the correlates results," Gilbert says.

The results will show whether there is a specific antibody level that will let you say with confidence a new vaccine will work without testing it in tens of thousands of people, he says.

"Everyone in the field is waiting for those results to give more confidence in being able to approve other vaccines more quickly and more reliably. So, we're getting close. We're almost there, actually," Gilbert says.

For vaccine developers, that day can't come soon enough.

Copyright 2021 NPR. To see more, visit https://www.npr.org.

Tags: coronavirus antibodies  COVID-19 vaccine  COVID-19  antibodies  Treatments