@article{Riou2021a,
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 poorly studied. We assessed both neutralizing antibody and T cell responses in 44 South African COVID-19 patients infected either with B.1.351, now dominant in South Africa, or infected prior to its emergence (‘first wave'), to provide an overall measure of immune evasion. We show for the first time that robust spike-specific CD4 and CD8 T cell responses were detectable in B.1.351-infected patients, similar to first wave patients. Using peptides spanning only the B.1.351 mutated regions, we identified CD4 T cell responses targeting the wild type peptides in 12/22 (54.5{\%}) first wave patients, all of whom failed to recognize corresponding B.1.351-mutated peptides (p=0.0005). However, responses to the 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. First wave patients showed a 12.7 fold reduction in plasma neutralization of B.1.351. This study shows that despite loss of recognition of immunodominant CD4 epitope(s), overall CD4 and CD8 T cell responses to B.1.351 are preserved. These observations may explain why, despite substantial loss of neutralizing antibody activity against B.1.351, several vaccines have retained the ability to protect against severe COVID-19 disease. One Sentence Summary T cell immunity to SARS-CoV-2 B.1.351 is preserved despite some loss of variant epitope recognition by CD4 T cells. {\#}{\#}{\#} Competing Interest Statement The authors have declared no competing interest. {\#}{\#}{\#} Funding Statement We acknowledge funding from the South African Medical Research Council 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 and 222754]. CR and WAB are supported by the EDCTP2 programme of the European Union (EU) Horizon 2020 programme (TMA2017SF-1951-TB-SPEC to CR and TMA2016SF-1535-CaTCH-22 to WAB). CR is further supported by the National Institutes of Health (NIH) (R21AI148027). PLM is supported by the South African Research Chairs Initiative of the Department of Science and Innovation and the National Research Foundation (Grant No 9834). HM is supported by a National Research Foundation Postdoctoral Fellowship (Grant No 129614). RJW is supported by Francis Crick Institute which receives funding from Wellcome (FC0010218), UKRI (FC0010218) and CRUK (FC0010218). CR and RJW also receive support from Rosetrees Trust (M926). The authors or their institutions did not at any time receive payment or services from any other third party for any aspect of the submitted work. {\#}{\#}{\#} Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was approved by the University of Cape Town Human Research Ethics Committee (HREC: 207/2020 and R021/2020) and electronic or written informed consent was obtained from all participants. All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes The data that support the findings of this study are available from the corresponding authors, WAB and CR, upon reasonable request.},
author = {Riou, Catherine and Keeton, Roanne and Moyo-Gwete, Thandeka and Hermanus, Tandile and Kgagudi, Prudence and Baguma, Richard and Tegally, Houriiyah and Doolabh, Deelan and Iranzadeh, Arash and Tyers, Lynn and Mutavhatsindi, Hygon and Tincho, Marius B and Benede, Ntombi and Marais, Gert and Chinhoyi, Lionel R and Mennen, Mathilda and Skelem, Sango and du Bruyn, Elsa and Stek, Cari and de Oliveira, Tulio and Williamson, Carolyn and Moore, Penny L and Wilkinson, Robert J and {B Ntusi}, Ntobeko A and Burgers, Wendy A},
doi = {10.1101/2021.06.03.21258307},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Riou et al. - 2021 - Loss of recognition of SARS-CoV-2 B.1.351 variant spike epitopes but overall preservation of T cell immunity.pdf:pdf},
journal = {medRxiv},
keywords = {OA,fund{\_}ack,genomics{\_}fund{\_}ack,original},
mendeley-tags = {OA,fund{\_}ack,genomics{\_}fund{\_}ack,original},
month = {jun},
pages = {2021.06.03.21258307},
publisher = {Cold Spring Harbor Laboratory Press},
title = {{Loss of recognition of SARS-CoV-2 B.1.351 variant spike epitopes but overall preservation of T cell immunity}},
url = {https://doi.org/10.1101/2021.06.03.21258307},
year = {2021}
}

{"_id":"uHt6WaouCjMzenb6j","bibbaseid":"riou-keeton-moyogwete-hermanus-kgagudi-baguma-tegally-doolabh-etal-lossofrecognitionofsarscov2b1351variantspikeepitopesbutoverallpreservationoftcellimmunity-2021","author_short":["Riou, C.","Keeton, R.","Moyo-Gwete, T.","Hermanus, T.","Kgagudi, P.","Baguma, R.","Tegally, H.","Doolabh, D.","Iranzadeh, A.","Tyers, L.","Mutavhatsindi, H.","Tincho, M. B","Benede, N.","Marais, G.","Chinhoyi, L. R","Mennen, M.","Skelem, S.","du Bruyn, E.","Stek, C.","de Oliveira, T.","Williamson, C.","Moore, P. L","Wilkinson, R. J","B Ntusi, N. A","Burgers, W. A"],"bibdata":{"bibtype":"article","type":"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 poorly studied. We assessed both neutralizing antibody and T cell responses in 44 South African COVID-19 patients infected either with B.1.351, now dominant in South Africa, or infected prior to its emergence (‘first wave'), to provide an overall measure of immune evasion. We show for the first time that robust spike-specific CD4 and CD8 T cell responses were detectable in B.1.351-infected patients, similar to first wave patients. Using peptides spanning only the B.1.351 mutated regions, we identified CD4 T cell responses targeting the wild type peptides in 12/22 (54.5%) first wave patients, all of whom failed to recognize corresponding B.1.351-mutated peptides (p=0.0005). However, responses to the 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. First wave patients showed a 12.7 fold reduction in plasma neutralization of B.1.351. This study shows that despite loss of recognition of immunodominant CD4 epitope(s), overall CD4 and CD8 T cell responses to B.1.351 are preserved. These observations may explain why, despite substantial loss of neutralizing antibody activity against B.1.351, several vaccines have retained the ability to protect against severe COVID-19 disease. One Sentence Summary T cell immunity to SARS-CoV-2 B.1.351 is preserved despite some loss of variant epitope recognition by CD4 T cells. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement We acknowledge funding from the South African Medical Research Council 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 and 222754]. CR and WAB are supported by the EDCTP2 programme of the European Union (EU) Horizon 2020 programme (TMA2017SF-1951-TB-SPEC to CR and TMA2016SF-1535-CaTCH-22 to WAB). CR is further supported by the National Institutes of Health (NIH) (R21AI148027). PLM is supported by the South African Research Chairs Initiative of the Department of Science and Innovation and the National Research Foundation (Grant No 9834). HM is supported by a National Research Foundation Postdoctoral Fellowship (Grant No 129614). RJW is supported by Francis Crick Institute which receives funding from Wellcome (FC0010218), UKRI (FC0010218) and CRUK (FC0010218). CR and RJW also receive support from Rosetrees Trust (M926). The authors or their institutions did not at any time receive payment or services from any other third party for any aspect of the submitted work. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was approved by the University of Cape Town Human Research Ethics Committee (HREC: 207/2020 and R021/2020) and electronic or written informed consent was obtained from all participants. All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes The data that support the findings of this study are available from the corresponding authors, WAB and CR, upon reasonable request.","author":[{"propositions":[],"lastnames":["Riou"],"firstnames":["Catherine"],"suffixes":[]},{"propositions":[],"lastnames":["Keeton"],"firstnames":["Roanne"],"suffixes":[]},{"propositions":[],"lastnames":["Moyo-Gwete"],"firstnames":["Thandeka"],"suffixes":[]},{"propositions":[],"lastnames":["Hermanus"],"firstnames":["Tandile"],"suffixes":[]},{"propositions":[],"lastnames":["Kgagudi"],"firstnames":["Prudence"],"suffixes":[]},{"propositions":[],"lastnames":["Baguma"],"firstnames":["Richard"],"suffixes":[]},{"propositions":[],"lastnames":["Tegally"],"firstnames":["Houriiyah"],"suffixes":[]},{"propositions":[],"lastnames":["Doolabh"],"firstnames":["Deelan"],"suffixes":[]},{"propositions":[],"lastnames":["Iranzadeh"],"firstnames":["Arash"],"suffixes":[]},{"propositions":[],"lastnames":["Tyers"],"firstnames":["Lynn"],"suffixes":[]},{"propositions":[],"lastnames":["Mutavhatsindi"],"firstnames":["Hygon"],"suffixes":[]},{"propositions":[],"lastnames":["Tincho"],"firstnames":["Marius","B"],"suffixes":[]},{"propositions":[],"lastnames":["Benede"],"firstnames":["Ntombi"],"suffixes":[]},{"propositions":[],"lastnames":["Marais"],"firstnames":["Gert"],"suffixes":[]},{"propositions":[],"lastnames":["Chinhoyi"],"firstnames":["Lionel","R"],"suffixes":[]},{"propositions":[],"lastnames":["Mennen"],"firstnames":["Mathilda"],"suffixes":[]},{"propositions":[],"lastnames":["Skelem"],"firstnames":["Sango"],"suffixes":[]},{"propositions":["du"],"lastnames":["Bruyn"],"firstnames":["Elsa"],"suffixes":[]},{"propositions":[],"lastnames":["Stek"],"firstnames":["Cari"],"suffixes":[]},{"propositions":["de"],"lastnames":["Oliveira"],"firstnames":["Tulio"],"suffixes":[]},{"propositions":[],"lastnames":["Williamson"],"firstnames":["Carolyn"],"suffixes":[]},{"propositions":[],"lastnames":["Moore"],"firstnames":["Penny","L"],"suffixes":[]},{"propositions":[],"lastnames":["Wilkinson"],"firstnames":["Robert","J"],"suffixes":[]},{"propositions":[],"lastnames":["B Ntusi"],"firstnames":["Ntobeko","A"],"suffixes":[]},{"propositions":[],"lastnames":["Burgers"],"firstnames":["Wendy","A"],"suffixes":[]}],"doi":"10.1101/2021.06.03.21258307","file":":C$\\$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Riou et al. - 2021 - Loss of recognition of SARS-CoV-2 B.1.351 variant spike epitopes but overall preservation of T cell immunity.pdf:pdf","journal":"medRxiv","keywords":"OA,fund_ack,genomics_fund_ack,original","mendeley-tags":"OA,fund_ack,genomics_fund_ack,original","month":"jun","pages":"2021.06.03.21258307","publisher":"Cold Spring Harbor Laboratory Press","title":"Loss of recognition of SARS-CoV-2 B.1.351 variant spike epitopes but overall preservation of T cell immunity","url":"https://doi.org/10.1101/2021.06.03.21258307","year":"2021","bibtex":"@article{Riou2021a,\r\nabstract = {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 poorly studied. We assessed both neutralizing antibody and T cell responses in 44 South African COVID-19 patients infected either with B.1.351, now dominant in South Africa, or infected prior to its emergence (‘first wave'), to provide an overall measure of immune evasion. We show for the first time that robust spike-specific CD4 and CD8 T cell responses were detectable in B.1.351-infected patients, similar to first wave patients. Using peptides spanning only the B.1.351 mutated regions, we identified CD4 T cell responses targeting the wild type peptides in 12/22 (54.5{\\%}) first wave patients, all of whom failed to recognize corresponding B.1.351-mutated peptides (p=0.0005). However, responses to the 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. First wave patients showed a 12.7 fold reduction in plasma neutralization of B.1.351. This study shows that despite loss of recognition of immunodominant CD4 epitope(s), overall CD4 and CD8 T cell responses to B.1.351 are preserved. These observations may explain why, despite substantial loss of neutralizing antibody activity against B.1.351, several vaccines have retained the ability to protect against severe COVID-19 disease. One Sentence Summary T cell immunity to SARS-CoV-2 B.1.351 is preserved despite some loss of variant epitope recognition by CD4 T cells. {\\#}{\\#}{\\#} Competing Interest Statement The authors have declared no competing interest. {\\#}{\\#}{\\#} Funding Statement We acknowledge funding from the South African Medical Research Council 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 and 222754]. CR and WAB are supported by the EDCTP2 programme of the European Union (EU) Horizon 2020 programme (TMA2017SF-1951-TB-SPEC to CR and TMA2016SF-1535-CaTCH-22 to WAB). CR is further supported by the National Institutes of Health (NIH) (R21AI148027). PLM is supported by the South African Research Chairs Initiative of the Department of Science and Innovation and the National Research Foundation (Grant No 9834). HM is supported by a National Research Foundation Postdoctoral Fellowship (Grant No 129614). RJW is supported by Francis Crick Institute which receives funding from Wellcome (FC0010218), UKRI (FC0010218) and CRUK (FC0010218). CR and RJW also receive support from Rosetrees Trust (M926). The authors or their institutions did not at any time receive payment or services from any other third party for any aspect of the submitted work. {\\#}{\\#}{\\#} Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was approved by the University of Cape Town Human Research Ethics Committee (HREC: 207/2020 and R021/2020) and electronic or written informed consent was obtained from all participants. All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes The data that support the findings of this study are available from the corresponding authors, WAB and CR, upon reasonable request.},\r\nauthor = {Riou, Catherine and Keeton, Roanne and Moyo-Gwete, Thandeka and Hermanus, Tandile and Kgagudi, Prudence and Baguma, Richard and Tegally, Houriiyah and Doolabh, Deelan and Iranzadeh, Arash and Tyers, Lynn and Mutavhatsindi, Hygon and Tincho, Marius B and Benede, Ntombi and Marais, Gert and Chinhoyi, Lionel R and Mennen, Mathilda and Skelem, Sango and du Bruyn, Elsa and Stek, Cari and de Oliveira, Tulio and Williamson, Carolyn and Moore, Penny L and Wilkinson, Robert J and {B Ntusi}, Ntobeko A and Burgers, Wendy A},\r\ndoi = {10.1101/2021.06.03.21258307},\r\nfile = {:C$\\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Riou et al. - 2021 - Loss of recognition of SARS-CoV-2 B.1.351 variant spike epitopes but overall preservation of T cell immunity.pdf:pdf},\r\njournal = {medRxiv},\r\nkeywords = {OA,fund{\\_}ack,genomics{\\_}fund{\\_}ack,original},\r\nmendeley-tags = {OA,fund{\\_}ack,genomics{\\_}fund{\\_}ack,original},\r\nmonth = {jun},\r\npages = {2021.06.03.21258307},\r\npublisher = {Cold Spring Harbor Laboratory Press},\r\ntitle = {{Loss of recognition of SARS-CoV-2 B.1.351 variant spike epitopes but overall preservation of T cell immunity}},\r\nurl = {https://doi.org/10.1101/2021.06.03.21258307},\r\nyear = {2021}\r\n}\r\n","author_short":["Riou, C.","Keeton, R.","Moyo-Gwete, T.","Hermanus, T.","Kgagudi, P.","Baguma, R.","Tegally, H.","Doolabh, D.","Iranzadeh, A.","Tyers, L.","Mutavhatsindi, H.","Tincho, M. 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