Researchers pinpoint ‘correlates of protection’ for Moderna vaccine
In medical research parlance, these test results would be “surrogate markers” of vaccine effectiveness, replacing the need for the cold calculus of counting and comparing those who became infected against those who did not. Surrogate marker trials could be shorter and quicker.
For a two-dose vaccine like that of Moderna, a trial using similar surrogate marker tests might be able to generate sufficient data from each participant as early as two months after the first dose. From first participant to final analysis, such a trial might demonstrate that a vaccine is meeting correlate benchmarks in three to five months, depending on how many tests are ultimately required and how often the participants are tested. Importantly, fewer participants would be needed.
“We’re talking hundreds, not thousands, of vaccinees,” Gilbert said in an interview about the findings.
Since all four tests performed equally well, Gilbert said it is conceivable that a single assay, likely the neutralization test involving ACE2, might be sufficient in the future to predict how effective a vaccine will be.
“There is precedent for delineating just one marker,” Gilbert said. “Typically, you specify a benchmark for what equals success and get the regulators to agree that it is appropriate. Usually, it’s based on a single assay.”
Follow-up will be crucial
Surrogate marker trials would not be permitted unless the FDA approves them, and while scientists want to develop correlates of protection, there is no consensus yet to adopt them in trials of new vaccines against rapidly evolving SARS-CoV-2, the virus that causes COVID-19.
The correlates of protection used to measure neutralization of the virus did not involve testing with a live virus, but rather used a harmless “pseudovirus” studded with the same spike proteins found on SARS-CoV-2. While pseudovirus testing is commonly employed in virology, some experts may advocate for live virus testing if these markers are used it critical tests of vaccines.
Nevertheless, Gilbert is optimistic that these surrogate markers could be used to test the efficacy of vaccines — both current and future. Even though they were developed against viruses circulating last year, they could become useful in evaluating vaccine efficacy against variants. That includes the worrisome delta variant, which is more readily transmissible than others and has quickly come to dominate COVID-19 infections in the U.S.
“I think it is realistic to suspect that success will occur. There are many historical examples where, for pathogens with multiple variants, the correlates did apply across them. Yet it remains crucial that we also follow up any provisional decisions based on such assays with direct verification that the vaccines benefit individuals and the public against COVID-19,” Gilbert said.