Highly conserved, non-human-like, and cross-reactive SARS-CoV-2 T cell epitopes for COVID-19 vaccine design and validation

Abstract Natural and vaccine-induced SARS-CoV-2 immunity in humans has been described but correlates of protection are not yet defined. T cells support the SARS-CoV-2 antibody response, clear virus-infected cells, and may be required to block transmission. In this study, we identified peptide epitop...

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Autores principales:	Lauren M. Meyers, Andres H. Gutiérrez, Christine M. Boyle, Frances Terry, Bethany G. McGonnigal, Andres Salazar, Michael F. Princiotta, Wiliam D. Martin, Anne S. De Groot, Leonard Moise
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/d615a4694c9742dd8d5bff1c0123276c
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spelling	oai:doaj.org-article:d615a4694c9742dd8d5bff1c0123276c2021-12-02T17:15:24ZHighly conserved, non-human-like, and cross-reactive SARS-CoV-2 T cell epitopes for COVID-19 vaccine design and validation10.1038/s41541-021-00331-62059-0105https://doaj.org/article/d615a4694c9742dd8d5bff1c0123276c2021-05-01T00:00:00Zhttps://doi.org/10.1038/s41541-021-00331-6https://doaj.org/toc/2059-0105Abstract Natural and vaccine-induced SARS-CoV-2 immunity in humans has been described but correlates of protection are not yet defined. T cells support the SARS-CoV-2 antibody response, clear virus-infected cells, and may be required to block transmission. In this study, we identified peptide epitopes associated with SARS-CoV-2 T-cell immunity. Using immunoinformatic methods, T-cell epitopes from spike, membrane, and envelope were selected for maximal HLA-binding potential, coverage of HLA diversity, coverage of circulating virus, and minimal potential cross-reactivity with self. Direct restimulation of PBMCs collected from SARS-CoV-2 convalescents confirmed 66% of predicted epitopes, whereas only 9% were confirmed in naive individuals. However, following a brief period of epitope-specific T-cell expansion, both cohorts demonstrated robust T-cell responses to 97% of epitopes. HLA-DR3 transgenic mouse immunization with peptides co-formulated with poly-ICLC generated a potent Th1-skewed, epitope-specific memory response, alleviating safety concerns of enhanced respiratory disease associated with Th2 induction. Taken together, these epitopes may be used to improve our understanding of natural and vaccine-induced immunity, and to facilitate the development of T-cell-targeted vaccines that harness pre-existing SARS-CoV-2 immunity.Lauren M. MeyersAndres H. GutiérrezChristine M. BoyleFrances TerryBethany G. McGonnigalAndres SalazarMichael F. PrinciottaWiliam D. MartinAnne S. De GrootLeonard MoiseNature PortfolioarticleImmunologic diseases. AllergyRC581-607Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Vaccines, Vol 6, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Lauren M. Meyers Andres H. Gutiérrez Christine M. Boyle Frances Terry Bethany G. McGonnigal Andres Salazar Michael F. Princiotta Wiliam D. Martin Anne S. De Groot Leonard Moise Highly conserved, non-human-like, and cross-reactive SARS-CoV-2 T cell epitopes for COVID-19 vaccine design and validation
description	Abstract Natural and vaccine-induced SARS-CoV-2 immunity in humans has been described but correlates of protection are not yet defined. T cells support the SARS-CoV-2 antibody response, clear virus-infected cells, and may be required to block transmission. In this study, we identified peptide epitopes associated with SARS-CoV-2 T-cell immunity. Using immunoinformatic methods, T-cell epitopes from spike, membrane, and envelope were selected for maximal HLA-binding potential, coverage of HLA diversity, coverage of circulating virus, and minimal potential cross-reactivity with self. Direct restimulation of PBMCs collected from SARS-CoV-2 convalescents confirmed 66% of predicted epitopes, whereas only 9% were confirmed in naive individuals. However, following a brief period of epitope-specific T-cell expansion, both cohorts demonstrated robust T-cell responses to 97% of epitopes. HLA-DR3 transgenic mouse immunization with peptides co-formulated with poly-ICLC generated a potent Th1-skewed, epitope-specific memory response, alleviating safety concerns of enhanced respiratory disease associated with Th2 induction. Taken together, these epitopes may be used to improve our understanding of natural and vaccine-induced immunity, and to facilitate the development of T-cell-targeted vaccines that harness pre-existing SARS-CoV-2 immunity.
format	article
author	Lauren M. Meyers Andres H. Gutiérrez Christine M. Boyle Frances Terry Bethany G. McGonnigal Andres Salazar Michael F. Princiotta Wiliam D. Martin Anne S. De Groot Leonard Moise
author_facet	Lauren M. Meyers Andres H. Gutiérrez Christine M. Boyle Frances Terry Bethany G. McGonnigal Andres Salazar Michael F. Princiotta Wiliam D. Martin Anne S. De Groot Leonard Moise
author_sort	Lauren M. Meyers
title	Highly conserved, non-human-like, and cross-reactive SARS-CoV-2 T cell epitopes for COVID-19 vaccine design and validation
title_short	Highly conserved, non-human-like, and cross-reactive SARS-CoV-2 T cell epitopes for COVID-19 vaccine design and validation
title_full	Highly conserved, non-human-like, and cross-reactive SARS-CoV-2 T cell epitopes for COVID-19 vaccine design and validation
title_fullStr	Highly conserved, non-human-like, and cross-reactive SARS-CoV-2 T cell epitopes for COVID-19 vaccine design and validation
title_full_unstemmed	Highly conserved, non-human-like, and cross-reactive SARS-CoV-2 T cell epitopes for COVID-19 vaccine design and validation
title_sort	highly conserved, non-human-like, and cross-reactive sars-cov-2 t cell epitopes for covid-19 vaccine design and validation
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/d615a4694c9742dd8d5bff1c0123276c
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Highly conserved, non-human-like, and cross-reactive SARS-CoV-2 T cell epitopes for COVID-19 vaccine design and validation

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