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Cell Rep Med . Targets and cross-reactivity of human T cell recognition of common cold coronaviruses

tetano

Editor, Senior Moderator
Cell Rep Med


. 2023 May 29;101088.
doi: 10.1016/j.xcrm.2023.101088. Online ahead of print. Targets and cross-reactivity of human T cell recognition of common cold coronaviruses

Alison Tarke[SUP] 1 [/SUP], Yun Zhang[SUP] 2 [/SUP], Nils Methot[SUP] 3 [/SUP], Tara M Narowski[SUP] 4 [/SUP], Elizabeth Phillips[SUP] 5 [/SUP], Simon Mallal[SUP] 5 [/SUP], April Frazier[SUP] 3 [/SUP], Gilberto Filaci[SUP] 6 [/SUP], Daniela Weiskopf[SUP] 3 [/SUP], Jennifer M Dan[SUP] 7 [/SUP], Lakshmanane Premkumar[SUP] 4 [/SUP], Richard H Scheuermann[SUP] 8 [/SUP], Alessandro Sette[SUP] 9 [/SUP], Alba Grifoni[SUP] 10 [/SUP]



Affiliations
Abstract

The coronavirus (CoV) family includes several viruses infecting humans, highlighting the importance of exploring pan-CoV vaccine strategies to provide broad adaptive immune protection. We analyze T cell reactivity against representative Alpha (NL63) and Beta (OC43) common cold CoVs (CCCs) in pre-pandemic samples. S, N, M, and nsp3 antigens are immunodominant, as shown for severe acute respiratory syndrome 2 (SARS2), while nsp2 and nsp12 are Alpha or Beta specific. We further identify 78 OC43- and 87 NL63-specific epitopes, and, for a subset of those, we assess the T cell capability to cross-recognize sequences from representative viruses belonging to AlphaCoV, sarbecoCoV, and Beta-non-sarbecoCoV groups. We find T cell cross-reactivity within the Alpha and Beta groups, in 89% of the instances associated with sequence conservation >67%. However, despite conservation, limited cross-reactivity is observed for sarbecoCoV, indicating that previous CoV exposure is a contributing factor in determining cross-reactivity. Overall, these results provide critical insights in developing future pan-CoV vaccines.

Keywords: CCC; Coronavirus; HuCoV; NL63; OC43; T cells; common cold; cross-reactivity; epitopes; sarbeco.

 
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