Development of a T cell-based immunodiagnostic system to effectively distinguish SARS-CoV-2 infection and COVID-19 vaccination status

• Published in: Cell host & microbe Vol. 30; no. 3; pp. 388 - 399.e3
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 09.03.2022
• Subjects: Antibodies, Viral; breakthrough infection; COVID-19; COVID-19 - diagnosis; COVID-19 Vaccines; epitope; Epitopes, T-Lymphocyte; Humans; immunodiagnostic tool; SARS-CoV-2; Spike Glycoprotein, Coronavirus; T cells; Vaccination; viruses; COVID-19; SARS-CoV-2; viruses; immunodiagnostic tool; breakthrough infection; T cells; epitope; vaccination
• ISSN: 1931-3128; 1934-6069; 1934-6069
• DOI: 10.1016/j.chom.2022.02.003

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. [Display omitted] •A T cell-based assay allows discrimination of SARS-CoV-2 infection and vaccination•The classification scheme has high sensitivity and specificity and broad applicability•The use of SARS-CoV-2 epitope pools yield higher accuracy than serological readouts•Breakthrough infections can be effectively segregated from vaccine responses Yu et al. developed an assay using epitope pools to effectively discriminate T cell responses of subjects based on their SARS-CoV-2 infection and COVID-19 vaccination history. This T cell-based classification scheme could potentially be used as an immunodiagnostic tool for longitudinal monitoring of vaccination responses and for establishing correlates of protection.