To understand the possibility of Covid-19 reinfection, researchers are working to create a blood test to define immunity to the virus and determine how long it lasts. As new variants arise and spread around the world, it is critical to know if—and when—the global population will need vaccine booster shots.
Now, a new study published last week in Nature Medicine presents evidence that a vaccine can effectively prevent coronavirus infections even if it only prompts about one-fifth of the antibody response that the average person has after a bout of Covid-19.
The findings are a major step toward identifying the level of coronavirus-neutralizing antibodies in the blood needed to protect a person from infection. Once researchers identify that level, called the correlate of protection, vaccine developers will be able to test their vaccines more quickly. The correlate of protection refers to the antibodies, B and T cells that can be measured in a blood test and act as a proxy for protection against a disease, Imperial College London immunologist Daniel Altmann tells Smriti Mallapaty at Nature News.
The correlate of protection is a standard tool in vaccine research. While it can be difficult to calculate at first, it could offer a boost to ending the pandemic, says University Medical Centre Hamburg-Eppendorf infectious disease expert Christine Dahlke to Graham Lawton at New Scientist.
"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. Biomedical Advanced Research and Development Authority, to Joe Palca at NPR.
Researchers are taking several approaches to figure out the correlate of protection for Covid-19.
A study published in the Journal of Clinical Microbiology in fall 2020 was the first to show that antibodies protect individuals against Covid-19. The evidence came from a fishing boat where an outbreak occurred, but three people who had previously been infected with the coronavirus—and had antibodies against it—did not become sick again, per New Scientist.
Now, Moderna, which developed a mRNA-based Covid-19 vaccine, is working with researchers to compare antibody levels between vaccinated people who do and do not get sick with Covid-19, reports NPR. The research team hopes to find out whether people who are vaccinated but still become infected, which is called a “breakthrough” infection, have lower immune system responses than people who don’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," says Houchens to NPR.
A separate experiment underway at the University of Oxford involves purposely exposing volunteers to the pandemic coronavirus. The volunteers had Covid-19 at some point before the trial, so they had some immune system activity already that the researchers will analyze.
“We’ll look at antibodies, T-cells, every aspect of immunity we can study,” says University of Oxford vaccinologist Helen McShane to New Scientist. “At its simplest, if we find that it is not possible to reinfect volunteers who have a certain level of antibody, then we have a correlate of protection.”
The new study published in Nature Medicine looks at the levels of neutralizing antibodies measured during the trials of seven vaccines that are now widely available. The study found mRNA-based vaccines like Moderna and Pfizer offer the longest-lasting antibody response.
But as the researchers note, neutralizing antibodies aren’t the immune system’s only defenses against a returning infection; memory B cells bide their time and spring into action to protect the body against future infections, John Timmer notes for Ars Technica. Future research into the correlate of protection could look at more parts of the immune system.
Once researchers identify the correlate of protection, though, vaccine development could happen much faster. Instead of running large-scale trials with tens of thousands of volunteers, some of whom catch Covid-19 during the course of the study, scientists could give trial vaccines to a smaller number of people and then run blood tests to see if their immune systems have activated enough to fight off the virus.
“Finding the correlate of protection has really been a holy grail for this disease, as for others,” says Altmann to Nature News. “It’s surprisingly hard to do.”