Escape from recognition of SARS-CoV-2 variant spike epitopes but overall preservation of T cell immunity.

Autor: Riou C; Wellcome Centre for Infectious Diseases Research in Africa, University of Cape Town, Observatory 7925, South Africa.; Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Observatory 7925, South Africa.; Division of Medical Virology, Department of Pathology, University of Cape Town, Observatory 7925, South Africa., Keeton R; Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Observatory 7925, South Africa.; Division of Medical Virology, Department of Pathology, University of Cape Town, Observatory 7925, South Africa., Moyo-Gwete T; National Institute for Communicable Diseases of the National Health Laboratory Services, Johannesburg, South Africa.; MRC Antibody Immunity Research Unit, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa., Hermanus T; National Institute for Communicable Diseases of the National Health Laboratory Services, Johannesburg, South Africa.; MRC Antibody Immunity Research Unit, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa., Kgagudi P; National Institute for Communicable Diseases of the National Health Laboratory Services, Johannesburg, South Africa.; MRC Antibody Immunity Research Unit, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa., Baguma R; Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Observatory 7925, South Africa.; Division of Medical Virology, Department of Pathology, University of Cape Town, Observatory 7925, South Africa., Valley-Omar Z; Division of Medical Virology, Department of Pathology, University of Cape Town, Observatory 7925, South Africa., Smith M; Division of Medical Virology, Department of Pathology, University of Cape Town, Observatory 7925, South Africa., Tegally H; KwaZulu-Natal Research Innovation and Sequencing Platform, Durban, South Africa., Doolabh D; Division of Medical Virology, Department of Pathology, University of Cape Town, Observatory 7925, South Africa., Iranzadeh A; Division of Medical Virology, Department of Pathology, University of Cape Town, Observatory 7925, South Africa., Tyers L; Division of Medical Virology, Department of Pathology, University of Cape Town, Observatory 7925, South Africa., Mutavhatsindi H; Wellcome Centre for Infectious Diseases Research in Africa, University of Cape Town, Observatory 7925, South Africa.; Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Observatory 7925, South Africa., Tincho MB; Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Observatory 7925, South Africa.; Division of Medical Virology, Department of Pathology, University of Cape Town, Observatory 7925, South Africa., Benede N; Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Observatory 7925, South Africa.; Division of Medical Virology, Department of Pathology, University of Cape Town, Observatory 7925, South Africa., Marais G; Division of Medical Virology, Department of Pathology, University of Cape Town, Observatory 7925, South Africa.; Groote Schuur Hospital Medical Virology Laboratory of the National Health Laboratory Service, Observatory 7925, South Africa., Chinhoyi LR; Department of Medicine, University of Cape Town and Groote Schuur Hospital, Observatory 7925, South Africa.; Hatter Institute for Cardiovascular Research in Africa, Faculty of Health Sciences, University of Cape Town, Observatory 7925, South Africa., Mennen M; Department of Medicine, University of Cape Town and Groote Schuur Hospital, Observatory 7925, South Africa.; Hatter Institute for Cardiovascular Research in Africa, Faculty of Health Sciences, University of Cape Town, Observatory 7925, South Africa., Skelem S; Department of Medicine, University of Cape Town and Groote Schuur Hospital, Observatory 7925, South Africa.; Hatter Institute for Cardiovascular Research in Africa, Faculty of Health Sciences, University of Cape Town, Observatory 7925, South Africa., du Bruyn E; Wellcome Centre for Infectious Diseases Research in Africa, University of Cape Town, Observatory 7925, South Africa.; Department of Medicine, University of Cape Town and Groote Schuur Hospital, Observatory 7925, South Africa., Stek C; Wellcome Centre for Infectious Diseases Research in Africa, University of Cape Town, Observatory 7925, South Africa.; Department of Medicine, University of Cape Town and Groote Schuur Hospital, Observatory 7925, South Africa.; Department of Infectious Diseases, Imperial College London, London W12 0NN, UK., de Oliveira T; KwaZulu-Natal Research Innovation and Sequencing Platform, Durban, South Africa., Williamson C; Wellcome Centre for Infectious Diseases Research in Africa, University of Cape Town, Observatory 7925, South Africa.; Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Observatory 7925, South Africa.; Division of Medical Virology, Department of Pathology, University of Cape Town, Observatory 7925, South Africa., Moore PL; National Institute for Communicable Diseases of the National Health Laboratory Services, Johannesburg, South Africa.; MRC Antibody Immunity Research Unit, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa., Wilkinson RJ; Wellcome Centre for Infectious Diseases Research in Africa, University of Cape Town, Observatory 7925, South Africa.; Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Observatory 7925, South Africa.; Department of Medicine, University of Cape Town and Groote Schuur Hospital, Observatory 7925, South Africa.; Department of Infectious Diseases, Imperial College London, London W12 0NN, UK.; The Francis Crick Institute, London NW1 1AT, UK., Ntusi NAB; Wellcome Centre for Infectious Diseases Research in Africa, University of Cape Town, Observatory 7925, South Africa.; Department of Medicine, University of Cape Town and Groote Schuur Hospital, Observatory 7925, South Africa.; Hatter Institute for Cardiovascular Research in Africa, Faculty of Health Sciences, University of Cape Town, Observatory 7925, South Africa., Burgers WA; Wellcome Centre for Infectious Diseases Research in Africa, University of Cape Town, Observatory 7925, South Africa.; Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Observatory 7925, South Africa.; Division of Medical Virology, Department of Pathology, University of Cape Town, Observatory 7925, South Africa.
Jazyk: angličtina
Zdroj: Science translational medicine [Sci Transl Med] 2022 Feb 09; Vol. 14 (631), pp. eabj6824. Date of Electronic Publication: 2022 Feb 09.
DOI: 10.1126/scitranslmed.abj6824
Abstrakt: SARS-CoV-2 variants that escape neutralization and potentially affect vaccine efficacy have emerged. T cell responses play a role in protection from reinfection and severe disease, but the potential for spike mutations to affect T cell immunity is incompletely understood. We assessed neutralizing antibody and T cell responses in 44 South African COVID-19 patients either infected with the Beta variant (dominant from November 2020 to May 2021) or infected before its emergence (first wave, Wuhan strain) to provide an overall measure of immune evasion. We show that robust spike-specific CD4 and CD8 T cell responses were detectable in Beta-infected patients, similar to first-wave patients. Using peptides spanning the Beta-mutated regions, we identified CD4 T cell responses targeting the wild-type peptides in 12 of 22 first-wave patients, all of whom failed to recognize corresponding Beta-mutated peptides. However, responses to mutated regions formed only a small proportion (15.7%) of the overall CD4 response, and few patients (3 of 44) mounted CD8 responses that targeted the mutated regions. Among the spike epitopes tested, we identified three epitopes containing the D215, L18, or D80 residues that were specifically recognized by CD4 T cells, and their mutated versions were associated with a loss of response. This study shows that despite loss of recognition of immunogenic CD4 epitopes, CD4 and CD8 T cell responses to Beta are preserved overall. These observations may explain why several vaccines have retained the ability to protect against severe COVID-19 even with substantial loss of neutralizing antibody activity against Beta.
Databáze: MEDLINE