Longitudinal analysis to determine persistence of T cell responses induced by SARS-CoV-2 vaccination, natural infection with SARS-CoV-2, and human common cold coronaviruses

Project Summary: Project 1 The current LJI HIPC Proposal focuses on common pathogens causing infectious diseases of the respiratory tract. Here in Project 1, our focus is to define changes of antigen-specific T cell responses to SARS-CoV-2 vaccination over time, up to 3 years post vaccination; and compare them to those observed in natural infection or previously-infected, but now recently-vaccinated subjects. We will examine T cell phenotypes defined by cytometric analysis of reference panels of markers. T cell sub- populations defined by transcriptomes of single-cells, and T cell clonality defined by single-cell T cell receptor (TCR) sequence analysis. These unbiased studies will define features associated with the magnitude and persistence of antigen-specific T cell responses. The data generated in the context of SARS-CoV-2 will then be compared the data to T cell responses induced by natural infection with common cold coronaviruses (CCC). This will provide a comparator with other much less pathogenic coronaviruses. Our studies will further detail and compare the results of vaccination with different SARS-CoV-2 vaccine platforms (Moderna, Pfizer, J&J and others that might be authorized). In parallel, we will investigate samples from two studies involving two commonly utilized vaccines, namely those against Yellow Fever and Pertussis. Finally, our studies will also provide a large cross-sectional cohort, to address, on one hand, differences in disease severity, ranging from mild to moderate to severe, and the impact of variables such as age, sex, ethnicity, disease severity, and exposure to CCC viruses on the magnitude and persistence of vaccine-induced T cell responses.