The Impact of Viral Mutations on Recognition by SARS-CoV-2 Specific T-Cells

We identify amino acid variants within dominant SARS-CoV-2 T-cell epitopes by interrogating global sequence data. Several variants within nucleocapsid and ORF3a epitopes have arisen independently in multiple lineages and result in loss of recognition by epitope-specific T-cells assessed by IFN-γ and cytotoxic killing assays. These data demonstrate the potential for T-cell evasion and highlight the need for ongoing surveillance for variants capable of escaping T-cell as well as humoral immunity.Funding: This work is supported by the UK Medical Research Council (MRC); Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (CIFMS), China; National Institute of Health Research (NIHR) Oxford Biomedical Research Centre and by UK Research and Innovation (UKRI)/NIHR through the UK Coronavirus Immunology Consortium (UK-CIC). Sequencing of SARS-CoV-2 samples and collation of data was undertaken by the COG-UK CONSORTIUM. COG-UK is supported by funding from the Medical Research Council (MRC) part of UK Research & Innovation (UKRI), the National Institute of Health Research (NIHR) and Genome Research Limited, operating as the Wellcome Sanger Institute. TIdS is supported by a Wellcome Trust Intermediate Clinical Fellowship (110058/Z/15/Z). MDP is funded by the NIHR Sheffield Biomedical Research Centre (BRC – IS-BRC-1215-20017). JCK is a Wellcome Investigator (WT204969/Z/16/Z) and supported by NIHR Oxford Biomedical Research Centre and CIFMS. The views expressed are those of the authors and not necessarily those of the NIHR, or MRC.Conflict of Interest: The authors declare no competing interests.Ethical Approval: Cryopreserved PBMCs were used from SARS-CoV-2 recovered donors recruited into the Sepsis Immunomics study with ethical approval from the South Central - Oxford C Research Ethics Committee in England (Ref 13/SC/0149).