Cutting Edge: Mouse SARS-CoV-2 Epitope Reveals Infection and Vaccine-Elicited CD8 T Cell Responses.

Joag, Vineet; Wijeyesinghe, Sathi; Stolley, J Michael; Quarnstrom, Clare F; Dileepan, Thamotharampillai; Soerens, Andrew G; Sangala, Jules A; O'Flanagan, Stephen D; Gavil, Noah V; Hong, Sung-Wook; Bhela, Siddheshvar; Gangadhara, Sailaja; Weyu, Eyob; Matchett, William E; Thiede, Joshua; Krishna, Venkatramana; Cheeran, Maxim C-J; Bold, Tyler D; Amara, Rama; Southern, Peter; Hart, Geoffrey T; Schifanella, Luca; Vezys, Vaiva; Jenkins, Marc K; Langlois, Ryan A; Masopust, David

The magnitude of SARS-CoV-2-specific T cell responses correlates inversely with human disease severity, suggesting T cell involvement in primary control. Whereas many COVID-19 vaccines focus on establishing humoral immunity to viral spike protein, vaccine-elicited T cell immunity may bolster durable protection or cross-reactivity with viral variants. To better enable mechanistic and vaccination studies in mice, we identified a dominant CD8 T cell SARS-CoV-2 nucleoprotein epitope. Infection of human ACE2 transgenic mice with SARS-CoV-2 elicited robust responses to H2-Db/N219-227, and 40% of HLA-A*02+ COVID-19 PBMC samples isolated from hospitalized patients responded to this peptide in culture. In mice, i.m. prime-boost nucleoprotein vaccination with heterologous vectors favored systemic CD8 T cell responses, whereas intranasal boosting favored respiratory immunity. In contrast, a single i.v. immunization with recombinant adenovirus established robust CD8 T cell memory both systemically and in the respiratory mucosa.