- Yu, Esther Dawen;
- Wang, Eric;
- Garrigan, Emily;
- Goodwin, Benjamin;
- Sutherland, Aaron;
- Tarke, Alison;
- Chang, James;
- Gálvez, Rosa Isela;
- Mateus, Jose;
- Ramirez, Sydney I;
- Rawlings, Stephen A;
- Smith, Davey M;
- Filaci, Gilberto;
- Frazier, April;
- Weiskopf, Daniela;
- Dan, Jennifer M;
- Crotty, Shane;
- Grifoni, Alba;
- Sette, Alessandro;
- da Silva Antunes, Ricardo
Both SARS-CoV-2 infections and COVID-19 vaccines elicit memory T cell responses. Here, we report the development of 2 pools of experimentally defined SARS-CoV-2 T cell epitopes that, in combination with spike, were used to discriminate 4 groups of subjects with different SARS-CoV-2 infection and COVID-19 vaccine status. The overall T cell-based classification accuracy was 89.2% and 88.5% in the experimental and validation cohorts. This scheme was applicable to different mRNA vaccines and different lengths of time post infection/post vaccination and yielded increased accuracy when compared to serological readouts. T cell responses from breakthrough infections were also studied and effectively segregated from vaccine responses, with a combined performance of 86.6% across all 239 subjects from the 5 groups. We anticipate that a T cell-based immunodiagnostic scheme to classify subjects based on their vaccination and natural infection history will be an important tool for longitudinal monitoring of vaccinations and for establishing SARS-CoV-2 correlates of protection.