The Francis Crick Institute
s41586-022-04460-3.pdf (17.29 MB)

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

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journal contribution
posted on 2022-03-31, 09:47 authored by 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 du Bruyn, Mieke A Van Der Mescht, Zelda de Beer, Talita R de Villiers, Annie Bodenstein, Gretha van den 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 de Oliveira, Linda-Gail Bekker, Glenda Gray, Veronica Ueckermann, Theresa Rossouw, Michael T Boswell, Jinal Bihman, Penny L Moore, Alex Sigal, Ntobeko AB Ntusi, Wendy A Burgers, Catherine Riou
The SARS-CoV-2 Omicron variant has multiple Spike (S) protein mutations1,2 that contribute to 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. We assessed the ability of T cells to react with Omicron spike in participants who were vaccinated with Ad26.CoV2.S, BNT162b2, or unvaccinated convalescent COVID-19 patients (n=70). We found that 70-80% 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 to Beta and Delta variants, despite Omicron harboring considerably more mutations. In Omicron-infected hospitalized patients (n=19), there were comparable T cell responses to ancestral spike, nucleocapsid and membrane proteins to those patients hospitalized in previous waves dominated by the ancestral, Beta or Delta variants (n=49). Thus, despite Omicron's extensive mutations and reduced susceptibility to neutralizing antibodies, 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.


Rosetrees Trust (Grant ID: M926, Grant title: RT M926) Crick (Grant ID: 10218, Grant title: Wilkinson, R FC001218)