As Omicron dominates the COVID-19 landscape, scientists are urging the FDA to reconsider how the agency defines immune responses.
More than 60 scientists from across the United States have signed a letter to the U.S. Food and Drug Administration asking the agency to include T cells as a measurement of effectiveness for COVID-19 vaccines. Usually, vaccines’ effectiveness is measured by an antibody response, but scientists are pushing for T cells to be recognized as a factor in long-term vaccine success.
One signatory is E. John Wherry, the chair of the department of systems pharmacology and translational therapeutics at the University of Pennsylvania Perelman School of Medicine. Wherry notes that with many diseases, and with COVID-19 especially, there seems to be a lot of misunderstanding when it comes to the ability of vaccines to protect a person from disease vs. from simply being infected.
“It’s been pretty clear that the T-cell response has been pretty robust and pretty stable over time. And that the manifestation of… mild infection versus disease, would fit with the idea that antibodies protect and provide a barrier from virus getting in, whereas T-cells can protect from progression to severe disease,” said Wherry.
Now, as Omicron dominates the COVID-19 landscape, scientists are urging the FDA to reconsider how the agency defines immune responses. Potential new variants could still arise, and continuous booster shots are not feasible for all regions. The scientists who have signed this letter are petitioning for more research around COVID-19 that includes T cells, which have been largely ignored in big studies so far.
“If thorough data had been collected on the broader adaptive immune response – including (antibodies) and T-cells – since the beginning of the COVID-19 pandemic, we would better understand the risks posed by the emerging variants….Examining the T-cell response has applications for clinical diagnosis and management, evaluation of protective immunity and vaccine assessment,” the letter read.
So far, the pharma industry has focused almost entirely on antibodies. The Pfizer and Moderna mRNA vaccines help the body to produce antibodies against COVID-19. Regeneron Pharmaceuticals’ REGEN-COV monoclonal antibody drug received FDA Emergency Use Authorization to treat COVID-19 in hospitalized patients and as a preemptive, prophylactic treatment to prevent people from getting sick in the first place.
Similarly, AstraZeneca focused on antibodies. Its prophylactic Evusheld, a combination of monoclonal antibodies tixagevimab and cilgavimab, was approved by Health Canada as a pre-COVID exposure prophylactic treatment for patients with compromised immune systems or for patients who were not able to get the vaccine.
But while antibodies can help prevent infection, T cells, which assist with long-term recovery, have largely been left behind. T cells help stimulate B cells to make antibodies, and they can also turn into Memory CD8 T cells, which provide a long-lasting immune response.
Pioneer Adaptive Biotechnologies recognized the potential of T cells during the pandemic. In June 2020, Adaptive teamed up with Microsoft to make a database of de-identified blood samples of COVID-19 patients. Their goal was to measure and analyze the different immune responses—specifically, the T cell response to the virus.
“The scale and precision with which we are now able to decode the T cell response to the virus may fundamentally change our ability to recover from this pandemic and the way in which all viruses are studied in the future,” said Harlan Robins, chief scientific officer and co-founder of Adaptive.
As Adaptive and other companies continue to measure T cells, they have found that T cell responses are one of the big differentiators between different COVID-19 variants and different vaccines’ responses to them.
Beth Israel Deaconess Medical Center published a study evaluating the immunogenicity of Johnson and Johnson‘s COVID-19 vaccine. The study found that in the case of the Beta variant, which was dominant in South Africa for a time, J&J’s vaccine did not produce antibodies very well, but the T cell responses were still effective.
“It was a bit paradoxical. We know that the South African variant seemed to escape some neutralizing antibodies. Yet that vaccine did quite well in South Africa when you look at the hard endpoints of avoiding death or hospitalization,” said Lance Baldo, M.D., chief medical officer at Adaptive. “So, the theory was: Maybe if the antibodies aren’t providing as much protection as we expected, could it in fact be the T cells that are providing that protection?”
Wherry and the other signers hope their letter will help the FDA to make effective changes. The agency could standardize the immune response measurements required when companies submit data for vaccines. A better understanding of the vaccine could help the FDA and pharma companies make more effective vaccine schedules, better understand possible vaccine side effects and know when prophylactic measures are and are not helpful.
“Antibodies, again, are critically important, but the fact that these vaccines induce very strong T-cells and that’s keeping you out of the hospital, is something we’ve not probably done a good enough job messaging broadly and the FDA can help in that by highlighting and messaging the importance of measuring T-cells,” Wherry said.
