2021-12-29 · The SARS-CoV-2 Omicron variant has multiple Spike (S) protein mutations that contribute to escape from the neutralizing antibody responses, and reducing vaccine protection from infection. 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 or BNT162b2, and in 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 that of the Beta and Delta variants, despite Omicron harbouring considerably more mutations. Additionally, in Omicron-infected hospitalized patients (n = 19), there were comparable T cell responses to ancestral spike, nucleocapsid and membrane proteins to those found in patients hospitalized in previous waves dominated by the ancestral, Beta or Delta variants (n = 49). These results demonstrate that despite Omicron's extensive mutations and reduced susceptibility to neutralizing antibodies, the majority of T cell response, induced by vaccination or natural infection, cross-recognises the variant. Well-preserved T cell immunity to Omicron is likely to contribute to protection from severe COVID-19, supporting early clinical observations from South Africa.
### Competing Interest Statement
A. Sette is a consultant for Gritstone Bio, Flow Pharma, Arcturus Therapeutics, ImmunoScape, CellCarta, Avalia, Moderna, Fortress and Repertoire. All of the other authors declare no competing interests. LJI has filed for patent protection for various aspects of vaccine design and identification of specific epitopes.
### Funding Statement
Research reported in this publication was supported by the South African Medical Research Council (SA-MRC) with funds received from the South African Department of Science and Innovation, including grants 96825, SHIPNCD 76756 and DST/CON 0250/2012. This work was also supported by the Poliomyelitis Research Foundation (21/65) 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 222574). This project has been funded in whole or in part with Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under Contract No. 75N93021C00016 to A.S. and Contract No. 75N9301900065 to A.S, D.W. P.L.M. is supported by the South African Research Chairs Initiative of the Department of Science and Innovation and the National Research Foundation (NRF; Grant No 9834). W.A.B. and C.R. are supported by the EDCTP2 programme of the European Union's Horizon 2020 programme (TMA2017SF-1951-TB-SPEC to C.R. and TMA2016SF-1535-CaTCH-22 to W.A.B.). N.A.B.N acknowledges funding from the SA-MRC, MRC UK, NRF and the Lily and Ernst Hausmann Trust. A.S. acknowledges funding from the Bill and Melinda Gates award INV-018944, the NIH (AI138546) and the South African Medical Research Council. R.J.W. acknowledges funding from the Francis Crick Institute, which receives funding from Wellcome FC0010218, UKRI FC0010218 and CRUK FC0010218 and the Rosetrees Trust grant M926 (to C.R. and R.J.W.). For the purposes of open access, the authors have applied a CC-BY public copyright license to any author-accepted version arising from this submission.
### Author Declarations
I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.
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The study was approved by the University of Cape Town Human Research Ethics Committee (ref: HREC 190/2020 and 209/2020) and the University of the Witwatersrand Human Research Ethics Committee (Medical) (ref. M210429 and M210752), the Biomedical Research Ethics Committee at the University of KwaZulu-Natal (ref.BREC/00001275/2020) and the University of Pretoria Health Sciences Research Ethics Committee (ref. 247/2020).
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