Scientists unlock clues to determining how safe vaccinated people are from Covid-19

Imagine peering into people’s blood and being able to pick up a simple marker of exactly how well protected they are from Covid-19.

It’s a pressing goal for scientists who are still trying to understand what immunity to the coronavirus looks like, how robustly vaccines protect us over time, and how protected people are who’ve had and recovered from Covid-19.

Now, a year and a half into the pandemic, researchers are starting to flesh out exactly what these “correlates of protection” look like, a step that could help track the durability of immunity and speed the development of additional vaccines. In a preprint paper last week, a group of researchers from both academia and U.S. health agencies reported their findings of the immune correlates for Moderna’s Covid-19 vaccine. The study demonstrated the link between the level of antibodies in a person’s system and how protected they are against Covid-19, validating the hypothesis that antibodies could be used as a measure that signifies overall protection.

“We saw a very clear correlation that the higher the level of antibody produced by vaccines, the less likely you were to become sick with Covid-19,” said Christopher Houchens, one of the authors of the paper and a biologist at the U.S. Biomedical Advanced Research and Development Authority.

The team is working on similar studies for the other vaccines that received support from Operation Warp Speed, including Johnson & Johnson’s and AstraZeneca’s, while other research groups are investigating other vaccines used around the world. Additional recent studies have also pointed to using antibody levels as correlates of protection.

A key advantage of knowing the correlates of protection is potentially enabling the approval of future vaccines. The vaccines that are available now went through a slog of clinical trials involving tens of thousands of people. But with vaccines increasingly available, it’s harder to enlist volunteers to participate in a study in which they might receive a placebo. Most people would instead choose to get a shot they know works.

Going forward, depending on what sort of evidence regulatory agencies decide to require, vaccine makers could instead study their shots in a few hundred people. Scientists could settle on a particular antibody threshold that shots would have to induce in people to get the green light — if someone has enough antibodies to hit that level, they’re protected, while anything below it portends infection risk.

With some other infections, researchers haven’t determined the exact correlates, but have a rough estimate of how much antibody a person needs to be protected, and they use that level for regulatory decisions. Flu shots, for example, don’t have to go through clinical trials every year, but are instead authorized based in part on the quality of immune response they generate in much smaller studies.

“Knowing the correlates of protection is incredibly useful,” said virologist Angela Rasmussen of the University of Saskatchewan’s Vaccine and Infectious Disease Organization, who is not part of the research group studying immune correlates in Covid-19 vaccines. “It really helps us develop vaccine policies that maximize keeping people as safe as possible.”

The Food and Drug Administration did not respond to a question about the agency’s views on using correlates of protection to authorize future Covid-19 vaccines.

Establishing the immune correlates for a certain pathogen can help predict whether a vaccine will be effective or not, but really, protection isn’t binary. As biostatistician David Benkeser of Emory University and another of the study authors put it, people don’t go “from sitting duck to someone who’s completely protected from Covid.”

Rather, protection exists on a gradual scale, with people being more or less vulnerable to disease depending on their immune landscape. And indeed, the study focused on Moderna’s shot didn’t narrow in on a particular cliff where protection fell off entirely, but rather found that the higher level of antibodies someone had, the more protected they were. Put another way, the lower their antibody levels, or titers, the more likely they were to get a symptomatic breakthrough case of Covid-19.

Knowing that, researchers wouldn’t just be able to look at antibody titers and determine whether a vaccine is effective overall. Rather, they could use the titers produced in a group of vaccine recipients to extrapolate an estimated level of effectiveness of a particular vaccine, a measurement that’s normally established during clinical trials.

The new study also underscored the variability in people’s responses to vaccines. There are only a handful of authorized vaccines being put into arms around the world, but a range of factors, from age to body mass to genetics and beyond, can influence how our individual immune systems kick in when primed. Some people will simply have more robust responses than others.

Scientists generally caution against individuals relying on antibody tests to determine their own protection against Covid-19. The tests can be faulty at such a granular level, and, as the researchers behind the new correlates study acknowledged, only look at antibodies, not the other parts of the immune response — like B cells and T cells — that are also involved in keeping people protected from disease.

Still, the immune correlate studies could more broadly inform the discussion about when and whether people — or at least certain groups of people — should get a booster shot. The research groups are continuing to follow the study volunteers and will track their antibody levels. If they drop over time, and in turn there’s an increase in Covid-19 cases among those people, it could point to the level at which people should receive another shot.

“We can track these individuals and look at if their antibody titers start to go down, but we don’t know how far they have to go down at this point to say, ‘Well your risk of infection is significant enough that we would recommend a third vaccine,’” Houchens said.