Omicron BA.1 Mutations in SARS-CoV-2 Spike Lead to Reduced T-Cell Response in Vaccinated and Convalescent Individuals |
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Authors: | Maarten E Emmelot Martijn Vos Mardi C Boer Nynke Y Rots Jelle de Wit Ccile A C M van Els Patricia Kaaijk |
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Institution: | 1.Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), 3721 MA Bilthoven, The Netherlands; (M.E.E.); (M.V.); (M.C.B.); (N.Y.R.); (J.d.W.); (C.A.C.M.v.E.);2.Faculty of Veterinary Medicine, Utrecht University, 3584 CL Utrecht, The Netherlands |
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Abstract: | Omicron BA.1 variant can readily infect people with vaccine-induced or naturally acquired SARS-CoV-2 immunity facilitated by escape from neutralizing antibodies. In contrast, T-cell reactivity against the Omicron BA.1 variant seems relatively well preserved. Here, we studied the preexisting T cells elicited by either vaccination with the mRNA-based BNT162b2 vaccine or by natural infection with ancestral SARS-CoV-2 for their cross-reactive potential to 20 selected CD4+ T-cell epitopes of spike-protein-harboring Omicron BA.1 mutations. Although the overall memory CD4+ T-cell responses primed by the ancestral spike protein was still preserved generally, we show here that there is also a clear loss of memory CD4+ T-cell cross-reactivity to immunodominant epitopes across the spike protein due to Omicron BA.1 mutations. Complete or partial loss of preexisting T-cell responsiveness was observed against 60% of 20 nonconserved CD4+ T-cell epitopes predicted to be presented by a broad set of common HLA class II alleles. Monitoring such mutations in circulating strains helps predict which virus variants may escape previously induced cellular immunity and could be of concern. |
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Keywords: | SARS-CoV-2 Omicron BA 1 variant mutations T-cell response vaccination natural infection cross-reactivity immune escape CD4+ T-cell epitopes HLA motif prediction |
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