Cutting Edge: Mouse SARS-CoV-2 Epitope Reveals Infection and Vaccine-Elicited CD8 T Cell Responses
Vineet Joag, Sathi Wijeyesinghe, J. Michael Stolley, Clare F. Quarnstrom, Thamotharampillai Dileepan, Andrew G. Soerens, Jules Sangala, Stephen D. O’Flanagan, Noah Veis Gavil, Sung‐Wook Hong, Siddheshvar Bhela, Sailaja Gangadhara, Eyob Weyu, William E. Matchett, Joshua M. Thiede, Venkatramana D. Krishna, Maxim C.‐J. Cheeran, Tyler D. Bold, Rama Rao Amara, Peter J. Southern, Geoffrey T. Hart, Luca Schifanella, Vaiva Vezys, Marc K. Jenkins, Ryan A. Langlois, David Masopust
Abstract
Abstract 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.