Broad and strong memory CD4+ and CD8+ T cells induced by SARS-CoV-2 in UK convalescent individuals following COVID-19.
Peng Y., Mentzer AJ., Liu G., Yao X., Yin Z., Dong D., Dejnirattisai W., Rostron T., Supasa P., Liu C., López-Camacho C., Slon-Campos J., Zhao Y., Stuart DI., Paesen GC., Grimes JM., Antson AA., Bayfield OW., Hawkins DEDP., Ker D-S., Wang B., Turtle L., Subramaniam K., Thomson P., Zhang P., Dold C., Ratcliff J., Simmonds P., de Silva T., Sopp P., Wellington D., Rajapaksa U., Chen Y-L., Salio M., Napolitani G., Paes W., Borrow P., Kessler BM., Fry JW., Schwabe NF., Semple MG., Baillie JK., Moore SC., Openshaw PJM., Ansari MA., Dunachie S., Barnes E., Frater J., Kerr G., Goulder P., Lockett T., Levin R., Zhang Y., Jing R., Ho L-P., Oxford Immunology Network Covid-19 Response T cell Consortium None., ISARIC4C Investigators None., Cornall RJ., Conlon CP., Klenerman P., Screaton GR., Mongkolsapaya J., McMichael A., Knight JC., Ogg G., Dong T.
The development of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines and therapeutics will depend on understanding viral immunity. We studied T cell memory in 42 patients following recovery from COVID-19 (28 with mild disease and 14 with severe disease) and 16 unexposed donors, using interferon-γ-based assays with peptides spanning SARS-CoV-2 except ORF1. The breadth and magnitude of T cell responses were significantly higher in severe as compared with mild cases. Total and spike-specific T cell responses correlated with spike-specific antibody responses. We identified 41 peptides containing CD4+ and/or CD8+ epitopes, including six immunodominant regions. Six optimized CD8+ epitopes were defined, with peptide-MHC pentamer-positive cells displaying the central and effector memory phenotype. In mild cases, higher proportions of SARS-CoV-2-specific CD8+ T cells were observed. The identification of T cell responses associated with milder disease will support an understanding of protective immunity and highlights the potential of including non-spike proteins within future COVID-19 vaccine design.