WE ARE getting closer to answering one of the most important remaining questions in the pandemic: how can we quickly test whether somebody is immune to the virus?
This elusive measurement of immunity is known as the correlate of protection: a simple, surrogate appraisal of the entire immune response that tells you whether somebody is protected against disease or infection. “So, for example, you measure the number of antibodies in blood and find that if you have a specific number you are protected,” says Christine Dahlke at the University Medical Centre Hamburg-Eppendorf in Germany. That number is a correlate of protection, or CoP. We don’t yet have one for SARS-CoV-2, says Dahlke, but we urgently need one.
CoPs are a standard tool in vaccinology and, although difficult to nail down, we have established them for numerous conditions, including measles, influenza and hepatitis. Getting one for covid-19 would be a boost to our efforts to end the pandemic, says Dahlke. It would allow us to bypass big vaccine trials that compare a vaccine candidate against a placebo to see the difference in infection rates. Instead, we could do simpler and quicker tests that identify whether a vaccine elicits the CoP.
“A measure that shows if we are immune to covid-19 would help us deal with new variants swiftly”
Finding a CoP for SARS-CoV-2 is a pressing issue because, despite the unprecedented success in developing covid-19 vaccines through large-scale clinical trials, there are growing fears that this approach has run its course. As the pandemic progresses, such trials become increasingly difficult to perform, for two reasons.
First, finding volunteers who haven’t been vaccinated or infected and so are immunologically naive is hard. Second, giving unprotected people placebos when good vaccines exist is unethical. “We need a better approach,” says Dahlke.
A CoP would also help us to deal with new variants swiftly, says Salim Abdool Karim, co-chair of the South African Ministerial Advisory Committee on covid-19. You would take serum from the blood of a vaccinated person that passes the CoP threshold, and see if it neutralises the new variant. If it doesn’t, then we would probably need to tweak the vaccine. This saves time because we don’t want to reformulate vaccines for every new variant of concern if the current ones are still adequate.
A CoP can also make it easier to estimate levels of immunity in the population, according to Fengcai Zhu at the Jiangsu Province Center for Disease Control and Prevention in Nanjing, China.
We have known for some time that it may be possible to identify a CoP for SARS-CoV-2, thanks to a ship called American Dynasty that set out from Seattle on 13 May 2020 to trawl for hake in the Pacific Ocean. Although everyone was screened for covid-19 before departure, 104 of the 122 crew caught the virus at sea.
No one knows who brought the virus on board, but blood tests analysed by a team at the University of Washington in Seattle revealed that three of the people who didn’t catch covid-19 had antibodies to the virus from a prior infection.
This lack of new infection in those people who already had antibodies was the first direct evidence that antibodies can protect against covid-19.
There is now a growing belief that finding a CoP is imminent. “The data we need is coming out of the various clinical trials for vaccines,” says Amit Srivastava at Pfizer’s vaccine development unit in Pennsylvania. Many of the trials are doing immunological assays on volunteers because the manufacturers also want to get CoPs as quickly as possible.
While we don’t have the final answer yet, a CoP is likely to involve measuring the levels of antibodies and T-cells. Antibodies latch on to pathogens outside cells and get rid of them, while T-cells destroy virus-infected cells. Ideally, any immunity test would be based on the simplest possible measurement and be one that could be carried out by a family doctor.
As well as vaccine trials, an ongoing experiment that will help us get to this point is a “challenge study” at the University of Oxford, which will expose volunteers who have had covid-19 to SARS-CoV-2 in an attempt to reinfect them.
The point of this study is to determine what kind of immune response prevents reinfection, says chief investigator Helen McShane. “We’ll look at antibodies, T-cells, every aspect of immunity we can study. 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.”
That would be a big step forward, says Dahlke. “The world does not have enough vaccines, we need new vaccines,” she says. “Correlates of protection are urgently needed.”