Researchers at Gladstone Institutes have carried out a detailed survey of T cells before and after COVID-19 immunization. The team concludes, in eLife, that both the Pfizer and Moderna vaccines lead to the generation of long-term populations of T cells that can recognize multiple variants of the SARS-CoV-2 virus. But they also identified key differences in the T cell responses of individuals who had been infected with COVID-19 prior to vaccination compared to those who had never been infected.
“Overall, our data support the idea that vaccines are eliciting a very robust T cell response in healthy individuals,” says researcher Nadia Roan. “But they also suggest there may be some ways to improve them further, by getting more of the vaccine-elicited T cells to park themselves in the respiratory tract. It’s not just the number of T cells that matter; It’s the quality—whether the T cells are the type that can actively destroy virus-infected cells,” says Roan.
Roan turned to a technology called CyTOF that can measure the levels of nearly 40 different proteins on the surface and inside of T cells. This let her and her colleagues identify exactly which subsets of T cells were able to recognize SARS-CoV-2 before and after vaccination. The researchers used the approach to study blood samples from 11 people who had received an mRNA vaccine (either Pfizer/BioNTech or Moderna) against SARS-CoV-2. Blood samples were collected from each individual before vaccination, approximately 2 weeks after their first vaccine dose, and approximately 2 weeks after their second dose. Six of the individuals had also previously recovered from mild COVID-19.
In people who had never been infected with SARS-CoV-2, Roan and her colleagues found that the T cell response became stronger—in both quantity and quality of T cells—after the second vaccine dose. However, in those who had previously had a COVID-19 infection, there was little change between the first and second doses of the vaccine. The researchers also found that, while all individuals had a robust T cell response, T cells from those who had previously contracted COVID-19 had molecular markers suggesting the immune cells could last longer and migrate more effectively to the respiratory tract.