Focusing on conserved immunogenic regions results in broad breadth of Betacoronavirus virus T cell recognition 4148

Abstract Description The Coronavirus (CoV) family, particularly the betaCoV genus, includes subgenera capable of infecting humans, such as sarbecoCoV (SARS-CoV and SARS-CoV-2) and merbecoCoV (MERS-CoV). Given the ongoing risk of new CoV outbreaks, there is a growing need to explore pan-betaCoV vaccine concepts that provide adaptive immune protection. To assess the feasibility of eliciting cross-reactive T cell responses, we selected conserved regions from the SARS-CoV-2 proteome that are shared across CoVs and known to be immunogenic for CD4 and CD8 T cells in humans. Our approach integrated experimental data from IEDB (www.IEDB.org) and a selection of representative sequences encompassing the different BetaCoV subgenera. Per each T cell epitope selected, we calculated the sequence conservation score per each viral representative sequence selected to account for the highest diversity within the subgenera. Our analyses identified Conserved T cell Epitope Regions (CTER) encompassing one-tenth of the proteome with a high projected population. We employed a flow cytometry-based AIM assay to validate these findings, demonstrating that CTER-specific T cells could cross-recognize viral isolates from the Sarbeco, Merbeco, and Embeco subgenera more effectively than non-CTER regions. These results provide critical insights for enhancing the breadth of T cell recognition across betaCoVs. Funding Sources This study has been funded by the NIH/NIAD P01 AI168347 to A.G., Topic Categories Viral Immunology (VIR)