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Limited Recognition of Highly Conserved Regions of SARS-CoV-2

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posted on 22.06.2022, 04:56 authored by S Swaminathan, KE Lineburg, GR Ambalathingal, P Crooks, Emma GrantEmma Grant, SV Mohan, J Raju, A Panikkar, L Le Texier, ZWM Tong, KY Chew, MA Neller, KR Short, H Gowda, Stephanie GrasStephanie Gras, R Khanna, C Smith
Understanding the immune response to severe acute respiratory syndrome coronavirus (SARS-CoV-2) is critical to overcome the current coronavirus disease (COVID-19) pandemic. Efforts are being made to understand the potential cross-protective immunity of memory T cells, induced by prior encounters with seasonal coronaviruses, in providing protection against severe COVID-19. In this study we assessed T-cell responses directed against highly conserved regions of SARS-CoV-2. Epitope mapping revealed 16 CD81 T-cell epitopes across the nucleocapsid (N), spike (S), and open reading frame (ORF)3a proteins of SARS-CoV-2 and five CD81 T-cell epitopes encoded within the highly conserved regions of the ORF1ab polyprotein of SARS-CoV-2. Comparative sequence analysis showed high conservation of SARS-CoV-2 ORF1ab T-cell epitopes in seasonal coronaviruses. Paradoxically, the immune responses directed against the conserved ORF1ab epitopes were infrequent and subdominant in both convalescent and unexposed participants. This subdominant immune response was consistent with a low abundance of ORF1ab encoded proteins in SARS-CoV-2 infected cells. Overall, these observations suggest that while cross-reactive CD81 T cells likely exist in unexposed individuals, they are not common and therefore are unlikely to play a significant role in providing broad preexisting immunity in the community.


The authors would like to thanks Queensland Health Forensic & Scientific Services, Queensland Department of Health who provided the SARS-CoV-2 isolate QLD02. The authors would also like to thanks all the participants who took place in our study. We also thank Vivek Venkatram for helping us with Bioinformatics programming. This work was supported by generous donations to the QIMR Berghofer COVID-19 appeal, and the Medical Research Future Fund (MRFF, APP2005654). S.S. is supported by Australian Government Research Training Program Scholarship and is supported by QIMR Berghofer Top-Up Scholarship, E.J.G. was supported by an NHMRC CJ Martin Fellowship (#1110429) and is supported by an Australian Research Council DECRA (DE210101479), SVM is supported by QIMR-Berghofer and The University of Queensland scholarship, KRS is supported by an Australian Research Council DECRA (DE180100512), S.G. is supported by and NHMRC SRF (#1159272).


Publication Date



Microbiology Spectrum





Article Number

ARTN e02780-21




American Society for Microbiology



Rights Statement

© 2022 Swaminathan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.