The impact of viral mutations on recognition by SARS-CoV-2 specific T-cells

10.1101/2021.04.08.438904

bioRxiv

8th April 2021

Contributing to research themes:

This research has not been peer-reviewed, and has been posted on pre-print repository medRxiv. This is a preliminary report that should not be regarded as conclusive, guide clinical practice/health-related behaviour, or be reported in news media as established information.

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.

Author list:

Affiliations:

The Florey Institute for Host-Pathogen Interactions and Department of Infection, Immunity and Cardiovascular Disease, Medical School, University of Sheffield, Sheffield, UK.
Vaccines and Immunity Theme, Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine, Banjul, The Gambia.
Chinese Academy of Medical Sciences (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK.
MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
Beijing You’an Hospital, Capital Medical University, Beijing, China.
CAMS Key Laboratory of Tumor Immunology and Radiation Therapy, Xinjiang Tumor Hospital, Xinjiang Medical University, China.
Nuffield Department of Medicine, University of Oxford, NDM Research Building, Oxford, UK.
Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK
Sheffield Biomedical Research Centre, The University of Sheffield, Sheffield, UK.
Sheffield Bioinformatics Core, The University of Sheffield, Sheffield, UK.
NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK.
Centre For Tropical Medicine and Global Health, Nuffield Dept. of Clinical Medicine, University of Oxford, UK
Mahidol-Oxford Tropical Medicine Research Unit, Bangkok, Thailand
https://www.cogconsortium.uk
Division of Infection and Immunity, University College London, London, UK.

§ These authors contributed equally
* Co-corresponding authors: Thushan I. de Silva, Tao Dong

Authors:

Thushan I. de Silva^1,2§*, Guihai Liu^3,4,5§, Benjamin B Lindsey^1§, Danning Dong^3,4,6§, DhruvShah¹, Alexander J. Mentzer^7,8, Adrienn Angyal¹, Rebecca Brown¹, Matthew D. Parker^9,10, ZixiYing^3,4, Xuan Yao^3,4, Lance Turtle¹¹, Susanna Dunachie^12,13, COVID-19 Genomics UK (COGUK) Consortium¹⁴, Mala K. Maini¹⁵, Graham Ogg^3,4, Julian C. Knight^3,7,8, Yanchun Peng^3,4,Sarah L. Rowland-Jones^1,7, Tao Dong^3,4,7*.