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

Autor: Swaminathan S; QIMR Berghofer Centre for Immunotherapy and Vaccine Development and Translational and Human Immunology Laboratory, Department of Immunology, QIMR Berghofer Medical Research Institutegrid.1049.c, Brisbane, Queensland, Australia.; Faculty of Medicine, The University of Queenslandgrid.1003.2, Brisbane, Queensland, Australia., Lineburg KE; QIMR Berghofer Centre for Immunotherapy and Vaccine Development and Translational and Human Immunology Laboratory, Department of Immunology, QIMR Berghofer Medical Research Institutegrid.1049.c, Brisbane, Queensland, Australia., Ambalathingal GR; QIMR Berghofer Centre for Immunotherapy and Vaccine Development and Translational and Human Immunology Laboratory, Department of Immunology, QIMR Berghofer Medical Research Institutegrid.1049.c, Brisbane, Queensland, Australia., Crooks P; QIMR Berghofer Centre for Immunotherapy and Vaccine Development and Translational and Human Immunology Laboratory, Department of Immunology, QIMR Berghofer Medical Research Institutegrid.1049.c, Brisbane, Queensland, Australia., Grant EJ; Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe Universitygrid.1018.8, Melbourne, Victoria, Australia.; Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia., Mohan SV; Faculty of Medicine, The University of Queenslandgrid.1003.2, Brisbane, Queensland, Australia.; Cancer Precision Medicine Group, QIMR Berghofer Medical Research Institutegrid.1049.c, Herston, Queensland, Australia., Raju J; QIMR Berghofer Centre for Immunotherapy and Vaccine Development and Translational and Human Immunology Laboratory, Department of Immunology, QIMR Berghofer Medical Research Institutegrid.1049.c, Brisbane, Queensland, Australia., Panikkar A; QIMR Berghofer Centre for Immunotherapy and Vaccine Development and Translational and Human Immunology Laboratory, Department of Immunology, QIMR Berghofer Medical Research Institutegrid.1049.c, Brisbane, Queensland, Australia., Le Texier L; QIMR Berghofer Centre for Immunotherapy and Vaccine Development and Translational and Human Immunology Laboratory, Department of Immunology, QIMR Berghofer Medical Research Institutegrid.1049.c, Brisbane, Queensland, Australia., Tong ZWM; School of Chemistry and Molecular Biosciences, The University of Queenslandgrid.1003.2, Brisbane, Queensland, Australia., Chew KY; School of Chemistry and Molecular Biosciences, The University of Queenslandgrid.1003.2, Brisbane, Queensland, Australia., Neller MA; QIMR Berghofer Centre for Immunotherapy and Vaccine Development and Translational and Human Immunology Laboratory, Department of Immunology, QIMR Berghofer Medical Research Institutegrid.1049.c, Brisbane, Queensland, Australia., Short KR; School of Chemistry and Molecular Biosciences, The University of Queenslandgrid.1003.2, Brisbane, Queensland, Australia., Gowda H; Faculty of Medicine, The University of Queenslandgrid.1003.2, Brisbane, Queensland, Australia.; Cancer Precision Medicine Group, QIMR Berghofer Medical Research Institutegrid.1049.c, Herston, Queensland, Australia., Gras S; Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe Universitygrid.1018.8, Melbourne, Victoria, Australia.; Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia., Khanna R; QIMR Berghofer Centre for Immunotherapy and Vaccine Development and Translational and Human Immunology Laboratory, Department of Immunology, QIMR Berghofer Medical Research Institutegrid.1049.c, Brisbane, Queensland, Australia.; Faculty of Medicine, The University of Queenslandgrid.1003.2, Brisbane, Queensland, Australia., Smith C; QIMR Berghofer Centre for Immunotherapy and Vaccine Development and Translational and Human Immunology Laboratory, Department of Immunology, QIMR Berghofer Medical Research Institutegrid.1049.c, Brisbane, Queensland, Australia.; Faculty of Medicine, The University of Queenslandgrid.1003.2, Brisbane, Queensland, Australia.
Jazyk: angličtina
Zdroj: Microbiology spectrum [Microbiol Spectr] 2022 Feb 23; Vol. 10 (1), pp. e0278021. Date of Electronic Publication: 2022 Feb 23.
DOI: 10.1128/spectrum.02780-21
Abstrakt: 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 CD8 + T-cell epitopes across the nucleocapsid (N), spike (S), and open reading frame (ORF)3a proteins of SARS-CoV-2 and five CD8 + 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 CD8 + 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. IMPORTANCE T cells play a critical role in protection against SARS-CoV-2. Despite being highly topical, the protective role of preexisting memory CD8 + T cells, induced by prior exposure to circulating common coronavirus strains, remains less clear. In this study, we established a robust approach to specifically assess T cell responses to highly conserved regions within SARS-CoV-2. Consistent with recent observations we demonstrate that recognition of these highly conserved regions is associated with an increased likelihood of milder disease. However, extending these observations we observed that recognition of these conserved regions is rare in both exposed and unexposed volunteers, which we believe is associated with the low abundance of these proteins in SARS-CoV-2 infected cells. These observations have important implications for the likely role preexisting immunity plays in controlling severe disease, further emphasizing the importance of vaccination to generate the immunodominant T cells required for immune protection.
Databáze: MEDLINE
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