T cell responses to SARS-CoV-2 spike cross-recognize Omicron

Roanne Keeton, Marius B. Tincho, Amkele Ngomti, Richard Baguma, Ntombi Benede, Akiko Suzuki, Khadija Khan, Sandile Cele, Mallory Bernstein, Farina Karim, Sharon V. Madzorera, Thandeka Moyo-Gwete, Mathilda Mennen, Sango Skelem, Marguerite Adriaanse, Daniel Mutithu, Olukayode Aremu, Cari Stek, Elsa Bruyn, Mieke A. Mescht, Zelda Beer, Talita R. Villiers, Annie Bodenstein, Gretha Berg, Adriano Mendes, Amy Strydom, Marietjie Venter, Jennifer Giandhari, Yeshnee Naidoo, Sureshnee Pillay, Houriiyah Tegally, Alba Grifoni, Daniela Weiskopf, Alessandro Sette, Robert J. Wilkinson, Tulio Oliveira, Linda-Gail Bekker, Glenda Gray, Veronica Ueckermann, Theresa Rossouw, Michael T. Boswell, Jinal N. Bhiman, Penny L. Moore, Alex Sigal, Ntobeko A. B. Ntusi, Wendy A. Burgers () and Catherine Riou ()
Additional contact information
Roanne Keeton: University of Cape Town, Observatory
Marius B. Tincho: University of Cape Town, Observatory
Amkele Ngomti: University of Cape Town, Observatory
Richard Baguma: University of Cape Town, Observatory
Ntombi Benede: University of Cape Town, Observatory
Akiko Suzuki: University of Cape Town, Observatory
Khadija Khan: Africa Health Research Institute
Sandile Cele: Africa Health Research Institute
Mallory Bernstein: Africa Health Research Institute
Farina Karim: Africa Health Research Institute
Sharon V. Madzorera: National Institute for Communicable Diseases of the National Health Laboratory Service
Thandeka Moyo-Gwete: National Institute for Communicable Diseases of the National Health Laboratory Service
Mathilda Mennen: University of Cape Town and Groote Schuur Hospital; Observatory
Sango Skelem: University of Cape Town and Groote Schuur Hospital; Observatory
Marguerite Adriaanse: University of Cape Town and Groote Schuur Hospital; Observatory
Daniel Mutithu: University of Cape Town and Groote Schuur Hospital; Observatory
Olukayode Aremu: University of Cape Town and Groote Schuur Hospital; Observatory
Cari Stek: University of Cape Town, Observatory
Elsa Bruyn: University of Cape Town, Observatory
Mieke A. Mescht: University of Pretoria
Zelda Beer: Tshwane District Hospital
Talita R. Villiers: Tshwane District Hospital
Annie Bodenstein: Tshwane District Hospital
Gretha Berg: Tshwane District Hospital
Adriano Mendes: University of Pretoria
Amy Strydom: University of Pretoria
Marietjie Venter: University of Pretoria
Jennifer Giandhari: University of KwaZulu-Natal
Yeshnee Naidoo: University of KwaZulu-Natal
Sureshnee Pillay: University of KwaZulu-Natal
Houriiyah Tegally: University of KwaZulu-Natal
Alba Grifoni: La Jolla Institute for Immunology
Daniela Weiskopf: La Jolla Institute for Immunology
Alessandro Sette: La Jolla Institute for Immunology
Robert J. Wilkinson: University of Cape Town, Observatory
Tulio Oliveira: University of KwaZulu-Natal
Linda-Gail Bekker: University of Cape Town, Observatory
Glenda Gray: South African Medical Research Council
Veronica Ueckermann: University of Pretoria and Steve Biko Academic Hospital
Theresa Rossouw: University of Pretoria
Michael T. Boswell: University of Pretoria and Steve Biko Academic Hospital
Jinal N. Bhiman: National Institute for Communicable Diseases of the National Health Laboratory Service
Penny L. Moore: University of Cape Town, Observatory
Alex Sigal: Africa Health Research Institute
Ntobeko A. B. Ntusi: University of Cape Town, Observatory
Wendy A. Burgers: University of Cape Town, Observatory
Catherine Riou: University of Cape Town, Observatory

Nature, 2022, vol. 603, issue 7901, 488-492

Abstract: Abstract The SARS-CoV-2 Omicron variant (B.1.1.529) has multiple spike protein mutations1,2 that contribute to viral escape from antibody neutralization3–6 and reduce vaccine protection from infection7,8. The extent to which other components of the adaptive response such as T cells may still target Omicron and contribute to protection from severe outcomes is unknown. Here we assessed the ability of T cells to react to Omicron spike protein in participants who were vaccinated with Ad26.CoV2.S or BNT162b2, or unvaccinated convalescent COVID-19 patients (n = 70). Between 70% and 80% of the CD4+ and CD8+ T cell response to spike was maintained across study groups. Moreover, the magnitude of Omicron cross-reactive T cells was similar for Beta (B.1.351) and Delta (B.1.617.2) variants, despite Omicron harbouring considerably more mutations. In patients who were hospitalized with Omicron infections (n = 19), there were comparable T cell responses to ancestral spike, nucleocapsid and membrane proteins to those in patients hospitalized in previous waves dominated by the ancestral, Beta or Delta variants (n = 49). Thus, despite extensive mutations and reduced susceptibility to neutralizing antibodies of Omicron, the majority of T cell responses induced by vaccination or infection cross-recognize the variant. It remains to be determined whether well-preserved T cell immunity to Omicron contributes to protection from severe COVID-19 and is linked to early clinical observations from South Africa and elsewhere9–12.

Date: 2022
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DOI: 10.1038/s41586-022-04460-3

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