Cellular immune responses to SARS CoV2 targets measured in humans recovered from COVID19 disease and in unexposed individuals

Highlights
•Measuring immunity to SARS-CoV-2 is key for understanding COVID19 and vaccine development
•Protein antigen (Epitope)  pools detect CD4+ and CD8+ T cells in 100 and 70% of convalescent COVID patients
•T cell responses are focused not only on virus spike but also on M, N and other ORFs
•T cell reactivity to SARS-CoV-2 targets is also detected in non-exposed individuals

Targets of T cell responses to SARS-CoV-2 coronavirus in humans with COVID-19 disease and unexposed individuals

Summary

Understanding adaptive immunity to SARS-CoV-2 is important for vaccine development, interpreting coronavirus disease 2019 (COVID-19) pathogenesis, and calibration of pandemic control measures. Using HLA class I and II predicted peptide ‘megapools’, circulating SARS-CoV-2−specific CD8+ and CD4+ T cells were identified in ∼70% and 100% of COVID-19 convalescent patients, respectively. CD4+ T cell responses to spike, the main target of most vaccine efforts, were robust and correlated with the magnitude of the anti-SARS-CoV-2 IgG and IgA titers. The M, spike and N proteins each accounted for 11-27% of the total CD4+ response, with additional responses commonly targeting nsp3, nsp4, ORF3a and ORF8, among others. For CD8+ T cells, spike and M were recognized, with at least eight SARS-CoV-2 ORFs targeted. Importantly, we detected SARS-CoV-2−reactive CD4+ T cells in ∼40-60% of unexposed individuals, suggesting cross-reactive T cell recognition between circulating ‘common cold’ coronaviruses and SARS-CoV-2.

Grifoni, A., Weiskopf, D., Ramirez, S.I., Mateus, J., Dan, J.M., Moderbacher, C.R., Rawlings, S.A., Sutherland, A., Premkumar, L., Jadi, R.S., Marrama, D., de Silva, A.M., Frazier, A., Carlin, A., Greenbaum, J.A., Peters, B., Krammer, F., Smith, D.M., Crotty, S., Sette, A., Targets of T cell responses to SARS-CoV-2 coronavirus in humans with COVID-19 disease and unexposed individuals, Cell (2020), doi: https://doi.org/10.1016/j.cell.2020.05.015.