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SARS-CoV-2 vaccination creates a strong, persistent T-cell response Memphis, Tennessee
Scientists have harnessed T cells 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 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."
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.
"That is a huge response that has largely been missed," she said.
These findings paint a more hopeful picture of lasting immune response to vaccination. While circulating T-cell responses (measured in the blood) might wane in six months, the researchers found that the T cells were still present and active in the lymph nodes, often at levels matching the peak of the response. Additionally, the part of the virus that the T cells are reacting to was not altered in the major SARS-CoV2 variants, including the delta and omicron variants. The approach used in this work could also be used to better understand the T-cell response to other infectious viruses such as influenza.
"An important aspect of this study is that the T cells are showing a stable response," said co-first author Mikhail Pogorelyy, Ph.D., St. Jude Department of Immunology. "Six months after vaccination the immune system is still very active, and the T cells in the lymph node are present at the same level as immediately after vaccination. We haven't been appreciating the whole story about what the immune system is doing."
St. Jude Children's Research Hospital
St. Jude Children's Research Hospital is leading the way the world understands, treats and cures childhood cancer and other life-threatening diseases. It is the only National Cancer Institute-designated Comprehensive Cancer Center devoted solely to children. Treatments developed at St. Jude have helped push the overall childhood cancer survival rate from 20% to 80% since the hospital opened more than 50 years ago. St. Jude freely shares the breakthroughs it makes, and every child saved at St. Jude means doctors and scientists worldwide can use that knowledge to save thousands more children. To learn more, visit stjude.org .