The T Cell Epitope Landscape of SARS-CoV-2 Variants of Concern

During the COVID-19 pandemic, several SARS-CoV-2 variants of concern (VOC) emerged, bringing with them varying degrees of health and socioeconomic burdens. In particular, the Omicron VOC displayed distinct features of increased transmissibility accompanied by antigenic drift in the spike protein that partially circumvented the ability of pre-existing antibody responses in the global population to neutralize the virus. However, T cell immunity has remained robust throughout all the different VOC transmission waves and has emerged as a critically important correlate of protection against SARS-CoV-2 and its VOCs, in both vaccinated and infected individuals. Therefore, as SARS-CoV-2 VOCs continue to evolve, it is crucial that we characterize the correlates of protection and the potential for immune escape for both B cell and T cell human immunity in the population. Generating the insights necessary to understand T cell immunity, experimentally, for the global human population is at present a critical but a time consuming, expensive, and laborious process. Further, it is not feasible to generate global or universal insights into T cell immunity in an actionable time frame for potential future emerging VOCs. However, using computational means we can expedite and provide early insights into the correlates of T cell protection. In this study, we generated and revealed insights on the T cell epitope landscape for the five main SARS-CoV-2 VOCs observed to date. We demonstrated using a unique AI prediction platform, a significant conservation of presentable T cell epitopes across all mutated peptides for each VOC. This was modeled using the most frequent HLA alleles in the human population and covers the most common HLA haplotypes in the human population. The AI resource generated through this computational study and associated insights may guide the development of T cell vaccines and diagnostics that are even more robust against current and future VOCs, and their emerging subvariants.