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

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Title: Escape from recognition of SARS-CoV-2 Beta variant spike epitopes but overall preservation of T cell immunity
Authors: Riou, C
Keeton, R
Moyo-Gwete, T
Hermanus, T
Kgagudi, P
Baguma, R
Valley-Omar, Z
Smith, M
Tegally, H
Doolabh, D
Iranzadeh, A
Tyers, L
Mutavhatsindi, H
Tincho, MB
Benede, N
Marais, G
Chinhoyi, LR
Mennen, M
Skelem, S
Du Bruyn, E
Stek, C
De Oliveira, T
Williamson, C
Moore, PL
Wilkinson, RJ
Ntusi, N
Burgers, WA
Item Type: Journal Article
Abstract: SARS-CoV-2 variants have emerged that escape neutralization and potentially impact vaccine efficacy. 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 infected either with the Beta variant (dominant from November 2020 to May 2021) or infected prior to 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 12/22 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 (3/44) 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 in spite of 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.
Issue Date: 21-Dec-2021
Date of Acceptance: 17-Dec-2021
URI: http://hdl.handle.net/10044/1/93531
DOI: 10.1126/scitranslmed.abj6824
ISSN: 1946-6234
Publisher: American Association for the Advancement of Science
Start Page: 1
End Page: 13
Journal / Book Title: Science Translational Medicine
Volume: 14
Issue: 631
Copyright Statement: © 2021, American Association for the Advancement of Science. This work is licensed under a Creative Commons Attribution 4.0 International (CC BY 4.0) license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/. This license does not apply to figures/photos/artwork or other content included in the article that is credited to a third party; obtain authorization from the rights holder before using such material.
Sponsor/Funder: Wellcome Trust
Funder's Grant Number: WDAI_P83556
Keywords: Antibodies, Viral
COVID-19
Epitopes
Humans
SARS-CoV-2
Spike Glycoprotein, Coronavirus
South African cellular immunity network
Humans
Antibodies, Viral
Epitopes
Spike Glycoprotein, Coronavirus
COVID-19
SARS-CoV-2
06 Biological Sciences
11 Medical and Health Sciences
Publication Status: Published
Online Publication Date: 2021-12-21
Appears in Collections:Department of Infectious Diseases
Faculty of Medicine
Imperial College London COVID-19



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