Identification of immunodominant T cell epitopes in SARS-CoV-2 spike protein in Syrian hamsters.

T cell immunity has a crucial role in vaccine-induced protection against respiratory viruses, yet a detailed characterization of T cell responses and epitopes in Syrian hamsters, a highly utilized preclinical, small animal model for SARS-CoV-2 research, is lacking. In this study, using an intranasal Chimpanzee adenoviral vectored vaccine (ChAd-SARS-CoV-2-S), we characterized the T cell response to the spike protein of SARS-CoV-2 in Syrian hamsters and identified immunogenic CD4+ and CD8+ T cell epitopes using IFN-γ ELISpot assays and cell depletions. The mucosal ChAd-SARS-CoV-2-S vaccine elicited strong T cell responses, with evidence of CD4+ and CD8+ T cell activation in both lymphoid and mucosal tissues. Responses were directed toward the non-receptor-binding domain regions of the spike protein, indicating that dominant T cell epitopes for hamsters reside elsewhere in this structural protein. Six different T cell epitopes (4 for CD4 and 2 for CD8) were identified in the spike protein, and epitope-specific responses were detected in hamsters from 2 vendors, suggesting genetic similarity in terms of major histocompatibility complex allele expression. Identifying T cell epitopes and characterizing T cell responses in lymphoid and mucosal compartments enhances the utility of Syrian hamsters as a preclinical model for SARS-CoV-2 vaccine studies.