Scientists have harnessed T-cell to better understand the immune response to mRNA vaccines against SARS-CoV-2, the virus that causes COVID-19. The findings from St. Jude Children’s Research Hospital and Washington University in St. Louis were published today in Cell.
The findings suggest that some aspects of the immune response to mRNA vaccines remain robust six months after vaccination.
Much of the research on immune response to mRNA vaccination has focused on antibody levels, which can be measured by a blood test. However, this is just one aspect of immunity. Researchers wanted to better understand the specificity and structure of the T-cell response to vaccination.
Researchers focused on a certain kind of T cells in the lymph nodes, which facilitate antibody development in vaccinated individuals. The team used samples from Washington University as well as from the St. Jude Tracking of Viral and Host Factors Associated with COVID-19 cohort. The cohort was established in 2020 with hospital St. Jude employees who volunteered to have their immune response to SARS-CoV-2 infection and vaccination monitored.
“Our study lays out a new way of discovering what the T-cell responses are directed against in SARS-CoV-2, and found a surprisingly large T-cell response that is likely shared by over half the world,” said co-corresponding author Paul Thomas, Ph.D., St. Jude Department of Immunology. “If your immune system is putting this much effort into seeing that particular piece of the virus, we need a better understanding of that interaction to get a full picture of how the immune system reacts to vaccination.”
A more detailed picture of immune response
Different people, and their T cells, identify different parts of the virus thanks in part to hypervariable T-cell receptors. The researchers created an analysis that uses T-cell receptors to guide the scientists to pieces of the virus that the immune system identifies most often. Called reverse epitope discovery, the analysis involves looking at clusters of highly similar T-cell receptors that recognize the virus in a similar way.
The study showed that half of the individuals studied reacted to the same part of the virus and that 10% of their CD4 T cells, which help coordinate the immune response, recognized this piece. That represents a significant T-cell response.
“In general, it is very challenging to track T-cell responses because there is so much diversity,” said co-first author Anastasia Minervina, Ph.D., St. Jude Department of Immunology. “We found a way to track the T cells and identified a dominant piece of the virus attracting immune attention in almost half the global population