Escape from recognition of SARS-CoV-2 variant spike epitopes but overall preservation of T cell immunity
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Escape from recognition of SARS-CoV-2 variant spike epitopes but overall preservation of T cell immunity. / Riou, Catherine; Keeton, Roanne; Moyo-Gwete, Thandeka; Hermanus, Tandile; Kgagudi, Prudence; Baguma, Richard; Valley-Omar, Ziyaad; Smith, Mikhail; Tegally, Houriiyah; Doolabh, Deelan; Iranzadeh, Arash; Tyers, Lynn; Mutavhatsindi, Hygon; Tincho, Marius B.; Benede, Ntombi; Marais, Gert; Chinhoyi, Lionel R.; Mennen, Mathilda; Skelem, Sango; du Bruyn, Elsa; Stek, Cari; de Oliveira, Tulio; Williamson, Carolyn; Moore, Penny L.; Wilkinson, Robert J.; Ntusi, Ntobeko A.B.; Burgers, Wendy A.; Abrahams, Fatima; Ayres, Frances; du Toit, Elloise; Goliath, Rene T.; Hanekom, Willem; Hardie, Diana; Hsiao, Nei Yuan; Kloverpris, Henrik; Korsman, Stephen; Lakay, Francisco; Lambson, Bronwen; Leslie, Alasdair; Makhado, Zanele; Maseko, Moepeng; Mhlanga, Donald; Naidoo, Michelle; Ndhlovu, Zaza; Ngomti, Amkele; Oosthuysen, Brent; Ruzive, Sheena; Sigal, Alex; Smith, Tamryn; van der Westhuizen, Dieter; South African Cellular Immunity Network.
In: Science Translational Medicine, Vol. 14, No. 631, eabj6824, 2022.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Escape from recognition of SARS-CoV-2 variant spike epitopes but overall preservation of T cell immunity
AU - Riou, Catherine
AU - Keeton, Roanne
AU - Moyo-Gwete, Thandeka
AU - Hermanus, Tandile
AU - Kgagudi, Prudence
AU - Baguma, Richard
AU - Valley-Omar, Ziyaad
AU - Smith, Mikhail
AU - Tegally, Houriiyah
AU - Doolabh, Deelan
AU - Iranzadeh, Arash
AU - Tyers, Lynn
AU - Mutavhatsindi, Hygon
AU - Tincho, Marius B.
AU - Benede, Ntombi
AU - Marais, Gert
AU - Chinhoyi, Lionel R.
AU - Mennen, Mathilda
AU - Skelem, Sango
AU - du Bruyn, Elsa
AU - Stek, Cari
AU - de Oliveira, Tulio
AU - Williamson, Carolyn
AU - Moore, Penny L.
AU - Wilkinson, Robert J.
AU - Ntusi, Ntobeko A.B.
AU - Burgers, Wendy A.
AU - Abrahams, Fatima
AU - Ayres, Frances
AU - du Toit, Elloise
AU - Goliath, Rene T.
AU - Hanekom, Willem
AU - Hardie, Diana
AU - Hsiao, Nei Yuan
AU - Kloverpris, Henrik
AU - Korsman, Stephen
AU - Lakay, Francisco
AU - Lambson, Bronwen
AU - Leslie, Alasdair
AU - Makhado, Zanele
AU - Maseko, Moepeng
AU - Mhlanga, Donald
AU - Naidoo, Michelle
AU - Ndhlovu, Zaza
AU - Ngomti, Amkele
AU - Oosthuysen, Brent
AU - Ruzive, Sheena
AU - Sigal, Alex
AU - Smith, Tamryn
AU - van der Westhuizen, Dieter
AU - South African Cellular Immunity Network
N1 - Funding Information: We thank the study participants and their families, and the clinical staff and personnel at Groote Schuur Hospital for their support and dedication. We thank the informal Variant consortium of South Africa, chaired by W. Hanekom and T. de Oliveira, for suggestions and discussion of data. For the purposes of open access, we have applied a CC BY public copyright license to any author-accepted version arising from this submission. This research was supported by the South African Medical Research Council, with funds received from the South African Department of Science and Innovation (DSI), and the Wellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa), which is supported by core funding from the Wellcome Trust (203135/Z/16/Z). C.R. and W.A.B. are supported by the EDCTP2 programme of the European Union (EU)'s Horizon 2020 programme (TMA2017SF-1951-TB-SPEC to C.R. and TMA2016SF-1535-CaTCH-22 to W.A.B.). This work is further supported by the National Institutes of Health (R21AI148027 to C.R.), Francis Crick Institute, which receives funding from Wellcome FC0010218, UKRI FC0010218, and CRUK FC0010218, and Rosetrees Trust grant M926 (to C.R. and R.J.W.). P.L.M. is supported by the South African Research Chairs Initiative of the DSI and the National Research Foundation (grant no. 9834). N.A.B.N. acknowledges funding from the SA-MRC, MRC UK, NRF, and the Lily and Ernst Hausmann Trust. H.M. is in part supported by the Fogarty International Center of the National Institutes of Health under Award Number D43 TW010559 Publisher Copyright: © 2022 The Authors, some rights reserved
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
U2 - 10.1126/scitranslmed.abj6824
DO - 10.1126/scitranslmed.abj6824
M3 - Journal article
C2 - 34931886
AN - SCOPUS:85122758808
VL - 14
JO - Science Translational Medicine
JF - Science Translational Medicine
SN - 1946-6234
IS - 631
M1 - eabj6824
ER -
ID: 322494674