Tags

Type your tag names separated by a space and hit enter

Identification of SARS-CoV-2 Nucleocapsid and Spike T-Cell Epitopes for Assessing T-Cell Immunity.
J Virol. 2021 02 24; 95(6)JV

Abstract

Developing optimal T-cell response assays to severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is critical for measuring the duration of immunity to this disease and assessing the efficacy of vaccine candidates. These assays need to target conserved regions of SARS-CoV-2 global variants and avoid cross-reactivity to seasonal human coronaviruses. To contribute to this effort, we employed an in silico immunoinformatics analysis pipeline to identify immunogenic peptides resulting from conserved and highly networked regions with topological importance from the SARS-CoV-2 nucleocapsid and spike proteins. A total of 57 highly networked T-cell epitopes that are conserved across geographic viral variants were identified from these viral proteins, with a binding potential to diverse HLA alleles and 80 to 100% global population coverage. Importantly, 18 of these T-cell epitope derived peptides had limited homology to seasonal human coronaviruses making them promising candidates for SARS-CoV-2-specific T-cell immunity assays. Moreover, two of the NC-derived peptides elicited effector/polyfunctional responses of CD8+ T cells derived from SARS-CoV-2 convalescent patients.IMPORTANCE The development of specific and validated immunologic tools is critical for understanding the level and duration of the cellular response induced by SARS-CoV-2 infection and/or vaccines against this novel coronavirus disease. To contribute to this effort, we employed an immunoinformatics analysis pipeline to define 57 SARS-CoV-2 immunogenic peptides within topologically important regions of the nucleocapsid (NC) and spike (S) proteins that will be effective for detecting cellular immune responses in 80 to 100% of the global population. Our immunoinformatics analysis revealed that 18 of these peptides had limited homology to circulating seasonal human coronaviruses and therefore are promising candidates for distinguishing SARS-CoV-2-specific immune responses from pre-existing coronavirus immunity. Importantly, CD8+ T cells derived from SARS-CoV-2 survivors exhibited polyfunctional effector responses to two novel NC-derived peptides identified as HLA-binders. These studies provide a proof of concept that our immunoinformatics analysis pipeline identifies novel immunogens which can elicit polyfunctional SARS-CoV-2-specific T-cell responses.

Authors+Show Affiliations

Centre for Virus Research, The Westmead Institute for Medical Research, Westmead, New South Wales, Australia eunok.lee@sydney.edu.au. Sydney Medical School, Faculty of Medicine and Health, The University of Sydney, Camperdown, New South Wales, Australia.Centre for Virus Research, The Westmead Institute for Medical Research, Westmead, New South Wales, Australia. Sydney Medical School, Faculty of Medicine and Health, The University of Sydney, Camperdown, New South Wales, Australia.Centre for Virus Research, The Westmead Institute for Medical Research, Westmead, New South Wales, Australia. Sydney Medical School, Faculty of Medicine and Health, The University of Sydney, Camperdown, New South Wales, Australia.Centre for Virus Research, The Westmead Institute for Medical Research, Westmead, New South Wales, Australia. Sydney Medical School, Faculty of Medicine and Health, The University of Sydney, Camperdown, New South Wales, Australia.Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia. QIMR Berghofer Centre for Immunotherapy and Vaccine Development, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.Centre for Virus Research, The Westmead Institute for Medical Research, Westmead, New South Wales, Australia. Sydney Medical School, Faculty of Medicine and Health, The University of Sydney, Camperdown, New South Wales, Australia. Centre for Infectious Diseases and Microbiology, The Westmead Institute for Medical Research, Westmead, New South Wales, Australia. Marie Bashir Institute for Infectious Diseases and Biosecurity, School of Life and Environmental Sciences and School of Medical Sciences, The University of Sydney, Westmead, New South Wales, Australia.Sydney Medical School, Faculty of Medicine and Health, The University of Sydney, Camperdown, New South Wales, Australia. Centre for Cancer Research, The Westmead Institute for Medical Research, Westmead, New South Wales, Australia. BMT and Cell Therapies Program, Westmead Hospital, Westmead, New South Wales, Australia.Sydney Medical School, Faculty of Medicine and Health, The University of Sydney, Camperdown, New South Wales, Australia. Centre for Cancer Research, The Westmead Institute for Medical Research, Westmead, New South Wales, Australia. BMT and Cell Therapies Program, Westmead Hospital, Westmead, New South Wales, Australia.Centre for Virus Research, The Westmead Institute for Medical Research, Westmead, New South Wales, Australia. Sydney Medical School, Faculty of Medicine and Health, The University of Sydney, Camperdown, New South Wales, Australia.Centre for Virus Research, The Westmead Institute for Medical Research, Westmead, New South Wales, Australia. Sydney Medical School, Faculty of Medicine and Health, The University of Sydney, Camperdown, New South Wales, Australia.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

33443088

Citation

Lee, Eunok, et al. "Identification of SARS-CoV-2 Nucleocapsid and Spike T-Cell Epitopes for Assessing T-Cell Immunity." Journal of Virology, vol. 95, no. 6, 2021.
Lee E, Sandgren K, Duette G, et al. Identification of SARS-CoV-2 Nucleocapsid and Spike T-Cell Epitopes for Assessing T-Cell Immunity. J Virol. 2021;95(6).
Lee, E., Sandgren, K., Duette, G., Stylianou, V. V., Khanna, R., Eden, J. S., Blyth, E., Gottlieb, D., Cunningham, A. L., & Palmer, S. (2021). Identification of SARS-CoV-2 Nucleocapsid and Spike T-Cell Epitopes for Assessing T-Cell Immunity. Journal of Virology, 95(6). https://doi.org/10.1128/JVI.02002-20
Lee E, et al. Identification of SARS-CoV-2 Nucleocapsid and Spike T-Cell Epitopes for Assessing T-Cell Immunity. J Virol. 2021 02 24;95(6) PubMed PMID: 33443088.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Identification of SARS-CoV-2 Nucleocapsid and Spike T-Cell Epitopes for Assessing T-Cell Immunity. AU - Lee,Eunok, AU - Sandgren,Kerrie, AU - Duette,Gabriel, AU - Stylianou,Vicki V, AU - Khanna,Rajiv, AU - Eden,John-Sebastian, AU - Blyth,Emily, AU - Gottlieb,David, AU - Cunningham,Anthony L, AU - Palmer,Sarah, Y1 - 2021/02/24/ PY - 2020/10/11/received PY - 2020/12/16/accepted PY - 2021/1/15/pubmed PY - 2021/3/6/medline PY - 2021/1/14/entrez KW - COVID-19 vaccines KW - SARS-CoV-2 KW - T-cell effector/polyfunctionality KW - diagnostic tools KW - highly networked/conserved T-cell epitope derived peptides KW - nucleocapsid and spike proteins KW - protein network JF - Journal of virology JO - J Virol VL - 95 IS - 6 N2 - Developing optimal T-cell response assays to severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is critical for measuring the duration of immunity to this disease and assessing the efficacy of vaccine candidates. These assays need to target conserved regions of SARS-CoV-2 global variants and avoid cross-reactivity to seasonal human coronaviruses. To contribute to this effort, we employed an in silico immunoinformatics analysis pipeline to identify immunogenic peptides resulting from conserved and highly networked regions with topological importance from the SARS-CoV-2 nucleocapsid and spike proteins. A total of 57 highly networked T-cell epitopes that are conserved across geographic viral variants were identified from these viral proteins, with a binding potential to diverse HLA alleles and 80 to 100% global population coverage. Importantly, 18 of these T-cell epitope derived peptides had limited homology to seasonal human coronaviruses making them promising candidates for SARS-CoV-2-specific T-cell immunity assays. Moreover, two of the NC-derived peptides elicited effector/polyfunctional responses of CD8+ T cells derived from SARS-CoV-2 convalescent patients.IMPORTANCE The development of specific and validated immunologic tools is critical for understanding the level and duration of the cellular response induced by SARS-CoV-2 infection and/or vaccines against this novel coronavirus disease. To contribute to this effort, we employed an immunoinformatics analysis pipeline to define 57 SARS-CoV-2 immunogenic peptides within topologically important regions of the nucleocapsid (NC) and spike (S) proteins that will be effective for detecting cellular immune responses in 80 to 100% of the global population. Our immunoinformatics analysis revealed that 18 of these peptides had limited homology to circulating seasonal human coronaviruses and therefore are promising candidates for distinguishing SARS-CoV-2-specific immune responses from pre-existing coronavirus immunity. Importantly, CD8+ T cells derived from SARS-CoV-2 survivors exhibited polyfunctional effector responses to two novel NC-derived peptides identified as HLA-binders. These studies provide a proof of concept that our immunoinformatics analysis pipeline identifies novel immunogens which can elicit polyfunctional SARS-CoV-2-specific T-cell responses. SN - 1098-5514 UR - https://www.unboundmedicine.com/medline/citation/33443088/Identification_of_SARS_CoV_2_Nucleocapsid_and_Spike_T_Cell_Epitopes_for_Assessing_T_Cell_Immunity_ L2 - https://journals.asm.org/doi/10.1128/JVI.02002-20?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -