Cargando…

LB-18. Broad and Prevalent SARS-CoV-2 CD8+ T Cell Response in Recovered COVID-19 Individuals Demonstrates Kinetics of Early Differentiation

BACKGROUND: Understanding the diversity, breadth, magnitude, and functional profile of the T cell response against SARS-CoV-2 in recovered COVID-19 individuals is critical to evaluate the contribution of T cells to produce a potentially protective immune response. METHODS: We used a multiplexed pept...

Descripción completa

Detalles Bibliográficos
Autores principales: Kared, Hassen, Bloch, Evan, Redd, Andrew, Nardin, Alessandra, Sumatoh, Hermi, Kairi, Faris, Carbajo, Daniel, Abel, Brian, Newell, Evan, Laeyendecker, Oliver, Bonny, Tania, Benner, Sarah, Pekosz, Andy, Tobian, Aaron, Quinn, Thomas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7776945/
http://dx.doi.org/10.1093/ofid/ofaa515.1915
_version_ 1783630796343476224
author Kared, Hassen
Bloch, Evan
Redd, Andrew
Nardin, Alessandra
Sumatoh, Hermi
Kairi, Faris
Carbajo, Daniel
Abel, Brian
Newell, Evan
Laeyendecker, Oliver
Bonny, Tania
Benner, Sarah
Pekosz, Andy
Tobian, Aaron
Quinn, Thomas
author_facet Kared, Hassen
Bloch, Evan
Redd, Andrew
Nardin, Alessandra
Sumatoh, Hermi
Kairi, Faris
Carbajo, Daniel
Abel, Brian
Newell, Evan
Laeyendecker, Oliver
Bonny, Tania
Benner, Sarah
Pekosz, Andy
Tobian, Aaron
Quinn, Thomas
author_sort Kared, Hassen
collection PubMed
description BACKGROUND: Understanding the diversity, breadth, magnitude, and functional profile of the T cell response against SARS-CoV-2 in recovered COVID-19 individuals is critical to evaluate the contribution of T cells to produce a potentially protective immune response. METHODS: We used a multiplexed peptide-MHC tetramer approach to screen a total of 408 SARS-CoV-2 candidate peptide epitopes for CD8+ T cell recognition in a cohort of 30 individuals recovered from COVID-19. The peptides spanned the whole viral genome and were restricted to six prevalent HLA alleles; T cells were simultaneously characterized by a 28-marker phenotypic panel. The evolution of the SARS-CoV-2 T cell responses was then statistically modeled against time from diagnosis, and in relation to humoral and inflammatory response. Workflow for Study. A multiplexed peptide-MHC tetramer approach was used to screen SARS-CoV-2 candidate peptide epitopes in a cohort of 30 COVID-19 recovered patients across 6 prevalent HLA alleles, and T cells profiled with a 28-marker phenotypic panel. [Image: see text] Multiplex tetramer screen. One representative COVID-19 recovered patient and one healthy donor were screened for HLA- relevant SARS-CoV-2 epitopes, as well as epitopes for CMV, EBV, Influenza, Adenovirus and MART-1. Shown are the frequencies of tetramer-positive CD8 T cells from 2 technical replicates per subject. [Image: see text] RESULTS: Almost all individuals screened showed a T cell response against SARS-CoV-2 (29/30): 132 SARS-CoV-2-specific CD8+ T cells hits were detected, corresponding to 52 unique reactive epitopes. Twelve of the 52 unique SARS-CoV-2-specific epitopes were recognized by more than 40% of the individuals screened, indicating high prevalence in the subjects. Importantly, these CD8+ T cell responses were directed against both structural and non-structural viral proteins, with the highest magnitude against nucleocapsid derived peptides, but without any antigen-driven bias in the phenotype of specific T cells. Overall, SARS-CoV-2 T cells showed specific states of differentiation (stem-cell memory and transitional memory), which differed from those of MART-1, influenza, CMV and EBV-specific T cells. UMAP visualization revealed a phenotypic profile of SARS-CoV-2-specific CD8 T cells in COVID-19 convalescent donors that is distinct from other viral specificities, such as influenza, CMV, EBV and Adenovirus. [Image: see text] SARS-CoV-2 epitope screening revealed CD8+ T cell responses directed against both structural and non-structural viral proteins, with the highest magnitude response against nucleocapsid derived peptides [Image: see text] CONCLUSION: The kinetics modeling demonstrates a dynamic, evolving immune response characterized by a time-dependent decrease in overall inflammation, increase in neutralizing antibody titer, and progressive differentiation of a broad SARS-CoV-2 CD8 T cell response. It could be desirable to aim at recapitulating the hallmarks of this robust CD8 T cell response in the design of protective COVID-19 vaccines. DISCLOSURES: Hassen Kared, PhD, ImmunoScape (Shareholder) Alessandra Nardin, DvM, ImmunoScape (Shareholder) Hermi Sumatoh, BSc, Dip MTech, ImmunoScape (Shareholder) Faris Kairi, BSc, ImmunoScape (Shareholder) Daniel Carbajo, PhD, ImmunoScape (Shareholder) Brian Abel, PhD, MBA, ImmunoScape (Shareholder) Evan Newell, PhD, ImmunoScape (Shareholder)
format Online
Article
Text
id pubmed-7776945
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Oxford University Press
record_format MEDLINE/PubMed
spelling pubmed-77769452021-01-07 LB-18. Broad and Prevalent SARS-CoV-2 CD8+ T Cell Response in Recovered COVID-19 Individuals Demonstrates Kinetics of Early Differentiation Kared, Hassen Bloch, Evan Redd, Andrew Nardin, Alessandra Sumatoh, Hermi Kairi, Faris Carbajo, Daniel Abel, Brian Newell, Evan Laeyendecker, Oliver Bonny, Tania Benner, Sarah Pekosz, Andy Tobian, Aaron Quinn, Thomas Open Forum Infect Dis Late Breaker Abstracts BACKGROUND: Understanding the diversity, breadth, magnitude, and functional profile of the T cell response against SARS-CoV-2 in recovered COVID-19 individuals is critical to evaluate the contribution of T cells to produce a potentially protective immune response. METHODS: We used a multiplexed peptide-MHC tetramer approach to screen a total of 408 SARS-CoV-2 candidate peptide epitopes for CD8+ T cell recognition in a cohort of 30 individuals recovered from COVID-19. The peptides spanned the whole viral genome and were restricted to six prevalent HLA alleles; T cells were simultaneously characterized by a 28-marker phenotypic panel. The evolution of the SARS-CoV-2 T cell responses was then statistically modeled against time from diagnosis, and in relation to humoral and inflammatory response. Workflow for Study. A multiplexed peptide-MHC tetramer approach was used to screen SARS-CoV-2 candidate peptide epitopes in a cohort of 30 COVID-19 recovered patients across 6 prevalent HLA alleles, and T cells profiled with a 28-marker phenotypic panel. [Image: see text] Multiplex tetramer screen. One representative COVID-19 recovered patient and one healthy donor were screened for HLA- relevant SARS-CoV-2 epitopes, as well as epitopes for CMV, EBV, Influenza, Adenovirus and MART-1. Shown are the frequencies of tetramer-positive CD8 T cells from 2 technical replicates per subject. [Image: see text] RESULTS: Almost all individuals screened showed a T cell response against SARS-CoV-2 (29/30): 132 SARS-CoV-2-specific CD8+ T cells hits were detected, corresponding to 52 unique reactive epitopes. Twelve of the 52 unique SARS-CoV-2-specific epitopes were recognized by more than 40% of the individuals screened, indicating high prevalence in the subjects. Importantly, these CD8+ T cell responses were directed against both structural and non-structural viral proteins, with the highest magnitude against nucleocapsid derived peptides, but without any antigen-driven bias in the phenotype of specific T cells. Overall, SARS-CoV-2 T cells showed specific states of differentiation (stem-cell memory and transitional memory), which differed from those of MART-1, influenza, CMV and EBV-specific T cells. UMAP visualization revealed a phenotypic profile of SARS-CoV-2-specific CD8 T cells in COVID-19 convalescent donors that is distinct from other viral specificities, such as influenza, CMV, EBV and Adenovirus. [Image: see text] SARS-CoV-2 epitope screening revealed CD8+ T cell responses directed against both structural and non-structural viral proteins, with the highest magnitude response against nucleocapsid derived peptides [Image: see text] CONCLUSION: The kinetics modeling demonstrates a dynamic, evolving immune response characterized by a time-dependent decrease in overall inflammation, increase in neutralizing antibody titer, and progressive differentiation of a broad SARS-CoV-2 CD8 T cell response. It could be desirable to aim at recapitulating the hallmarks of this robust CD8 T cell response in the design of protective COVID-19 vaccines. DISCLOSURES: Hassen Kared, PhD, ImmunoScape (Shareholder) Alessandra Nardin, DvM, ImmunoScape (Shareholder) Hermi Sumatoh, BSc, Dip MTech, ImmunoScape (Shareholder) Faris Kairi, BSc, ImmunoScape (Shareholder) Daniel Carbajo, PhD, ImmunoScape (Shareholder) Brian Abel, PhD, MBA, ImmunoScape (Shareholder) Evan Newell, PhD, ImmunoScape (Shareholder) Oxford University Press 2020-12-31 /pmc/articles/PMC7776945/ http://dx.doi.org/10.1093/ofid/ofaa515.1915 Text en © The Author 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Late Breaker Abstracts
Kared, Hassen
Bloch, Evan
Redd, Andrew
Nardin, Alessandra
Sumatoh, Hermi
Kairi, Faris
Carbajo, Daniel
Abel, Brian
Newell, Evan
Laeyendecker, Oliver
Bonny, Tania
Benner, Sarah
Pekosz, Andy
Tobian, Aaron
Quinn, Thomas
LB-18. Broad and Prevalent SARS-CoV-2 CD8+ T Cell Response in Recovered COVID-19 Individuals Demonstrates Kinetics of Early Differentiation
title LB-18. Broad and Prevalent SARS-CoV-2 CD8+ T Cell Response in Recovered COVID-19 Individuals Demonstrates Kinetics of Early Differentiation
title_full LB-18. Broad and Prevalent SARS-CoV-2 CD8+ T Cell Response in Recovered COVID-19 Individuals Demonstrates Kinetics of Early Differentiation
title_fullStr LB-18. Broad and Prevalent SARS-CoV-2 CD8+ T Cell Response in Recovered COVID-19 Individuals Demonstrates Kinetics of Early Differentiation
title_full_unstemmed LB-18. Broad and Prevalent SARS-CoV-2 CD8+ T Cell Response in Recovered COVID-19 Individuals Demonstrates Kinetics of Early Differentiation
title_short LB-18. Broad and Prevalent SARS-CoV-2 CD8+ T Cell Response in Recovered COVID-19 Individuals Demonstrates Kinetics of Early Differentiation
title_sort lb-18. broad and prevalent sars-cov-2 cd8+ t cell response in recovered covid-19 individuals demonstrates kinetics of early differentiation
topic Late Breaker Abstracts
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7776945/
http://dx.doi.org/10.1093/ofid/ofaa515.1915
work_keys_str_mv AT karedhassen lb18broadandprevalentsarscov2cd8tcellresponseinrecoveredcovid19individualsdemonstrateskineticsofearlydifferentiation
AT blochevan lb18broadandprevalentsarscov2cd8tcellresponseinrecoveredcovid19individualsdemonstrateskineticsofearlydifferentiation
AT reddandrew lb18broadandprevalentsarscov2cd8tcellresponseinrecoveredcovid19individualsdemonstrateskineticsofearlydifferentiation
AT nardinalessandra lb18broadandprevalentsarscov2cd8tcellresponseinrecoveredcovid19individualsdemonstrateskineticsofearlydifferentiation
AT sumatohhermi lb18broadandprevalentsarscov2cd8tcellresponseinrecoveredcovid19individualsdemonstrateskineticsofearlydifferentiation
AT kairifaris lb18broadandprevalentsarscov2cd8tcellresponseinrecoveredcovid19individualsdemonstrateskineticsofearlydifferentiation
AT carbajodaniel lb18broadandprevalentsarscov2cd8tcellresponseinrecoveredcovid19individualsdemonstrateskineticsofearlydifferentiation
AT abelbrian lb18broadandprevalentsarscov2cd8tcellresponseinrecoveredcovid19individualsdemonstrateskineticsofearlydifferentiation
AT newellevan lb18broadandprevalentsarscov2cd8tcellresponseinrecoveredcovid19individualsdemonstrateskineticsofearlydifferentiation
AT laeyendeckeroliver lb18broadandprevalentsarscov2cd8tcellresponseinrecoveredcovid19individualsdemonstrateskineticsofearlydifferentiation
AT bonnytania lb18broadandprevalentsarscov2cd8tcellresponseinrecoveredcovid19individualsdemonstrateskineticsofearlydifferentiation
AT bennersarah lb18broadandprevalentsarscov2cd8tcellresponseinrecoveredcovid19individualsdemonstrateskineticsofearlydifferentiation
AT pekoszandy lb18broadandprevalentsarscov2cd8tcellresponseinrecoveredcovid19individualsdemonstrateskineticsofearlydifferentiation
AT tobianaaron lb18broadandprevalentsarscov2cd8tcellresponseinrecoveredcovid19individualsdemonstrateskineticsofearlydifferentiation
AT quinnthomas lb18broadandprevalentsarscov2cd8tcellresponseinrecoveredcovid19individualsdemonstrateskineticsofearlydifferentiation