High‐resolution analysis of individual spike peptide‐specific CD4+ T‐cell responses in vaccine recipients and COVID‐19 patients

Objectives Potential differences in the breadth, distribution and magnitude of CD4+ T‐cell responses directed against the SARS‐CoV‐2 spike glycoprotein between vaccinees, COVID‐19 patients and subjects who experienced both ways of immunisation have not been comprehensively compared on a peptide leve...

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Published inClinical & translational immunology Vol. 11; no. 8; pp. e1410 - n/a
Main Authors Karsten, Hendrik, Cords, Leon, Westphal, Tim, Knapp, Maximilian, Brehm, Thomas Theo, Hermanussen, Lennart, Omansen, Till Frederik, Schmiedel, Stefan, Woost, Robin, Ditt, Vanessa, Peine, Sven, Lütgehetmann, Marc, Huber, Samuel, Ackermann, Christin, Wittner, Melanie, Addo, Marylyn Martina, Sette, Alessandro, Sidney, John, Schulze zur Wiesch, Julian
Format Journal Article
LanguageEnglish
Published Australia John Wiley & Sons, Inc 2022
John Wiley and Sons Inc
Wiley
Subjects
Antibodies
B.1.1.529
CD4 antigen
CD4+ T cells
Coronaviruses
COVID-19
COVID-19 vaccines
Cytokines
Drb1 protein
Enzyme-linked immunosorbent assay
Glycoproteins
Histocompatibility antigen HLA
Infections
Interferon
Lymphocytes
MHC class II
Original
Patients
Peptides
SARS‐CoV‐2
Severe acute respiratory syndrome coronavirus 2
Spike glycoprotein
spike protein
Vaccination
vaccines
CD4+ T cells
MHC class II
B.1.1.529
SARS‐CoV‐2
vaccines
spike protein
Online AccessGet full text
ISSN2050-0068
2050-0068
DOI10.1002/cti2.1410

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Abstract Objectives Potential differences in the breadth, distribution and magnitude of CD4+ T‐cell responses directed against the SARS‐CoV‐2 spike glycoprotein between vaccinees, COVID‐19 patients and subjects who experienced both ways of immunisation have not been comprehensively compared on a peptide level. Methods Following virus‐specific in vitro cultivation, we determined the T‐cell responses directed against 253 individual overlapping 15‐mer peptides covering the entire SARS‐CoV‐2 spike glycoprotein using IFN‐γ ELISpot and intracellular cytokine staining. In vitro HLA binding was determined for selected peptides. Results We mapped 955 single peptide‐specific CD4+ T‐cell responses in a cohort of COVID‐19 patients (n = 8), uninfected vaccinees (n = 16) and individuals who experienced both infection and vaccination (n = 11). Patients and vaccinees (two‐time and three‐time vaccinees alike) had a comparable number of CD4+ T‐cell responses (median 26 vs. 29, P = 0.7289). Most of these specificities were conserved in B.1.1.529 and the BA.4 and BA.5 sublineages. The highest magnitude of these in vitro IFN‐γ CD4+ T‐cell responses was observed in COVID‐19 patients (median 0.35%), and three‐time vaccinees showed a higher magnitude than two‐time vaccinees (median 0.091% vs. 0.175%, P < 0.0001). Twelve peptide specificities were each detected in at least 40% of subjects. In vitro HLA binding showed promiscuous presentation by DRB1 molecules for several peptides. Conclusion Both SARS‐CoV‐2 infection and vaccination prime broadly directed T‐cell responses directed against the SARS‐CoV‐2 spike glycoprotein. This comprehensive high‐resolution analysis of spike peptide specificities will be a useful resource for further investigation of spike‐specific T‐cell responses. Individual CD4+ and CD8+ T‐cell responses directed against a total of 253 overlapping 15‐mer spike‐specific peptides were mapped in a cohort of COVID‐19 patients (n = 8), uninfected vaccinees (n = 16) and individuals who experienced both infection and vaccination (n = 11). We found that patients and vaccinees (two‐time and three‐time vaccinees alike) had a comparable number of CD4+ T‐cell responses (median 26 vs. 29, P = 0.7289) but differential magnitudes of these in vitro responses (median 0.35% vs. 0.12% IFN‐γ+ of CD4+ T cells, P < 0.0001). Most of the recognized specificities were conserved in the B.1.1.529 (omicron) Variant of Concern (VoC), and its sublineages and several peptides showed promiscuous presentation by DRB1 molecules in in vitro HLA‐binding assays.
AbstractList Objectives Potential differences in the breadth, distribution and magnitude of CD4+ T‐cell responses directed against the SARS‐CoV‐2 spike glycoprotein between vaccinees, COVID‐19 patients and subjects who experienced both ways of immunisation have not been comprehensively compared on a peptide level. Methods Following virus‐specific in vitro cultivation, we determined the T‐cell responses directed against 253 individual overlapping 15‐mer peptides covering the entire SARS‐CoV‐2 spike glycoprotein using IFN‐γ ELISpot and intracellular cytokine staining. In vitro HLA binding was determined for selected peptides. Results We mapped 955 single peptide‐specific CD4+ T‐cell responses in a cohort of COVID‐19 patients (n = 8), uninfected vaccinees (n = 16) and individuals who experienced both infection and vaccination (n = 11). Patients and vaccinees (two‐time and three‐time vaccinees alike) had a comparable number of CD4+ T‐cell responses (median 26 vs. 29, P = 0.7289). Most of these specificities were conserved in B.1.1.529 and the BA.4 and BA.5 sublineages. The highest magnitude of these in vitro IFN‐γ CD4+ T‐cell responses was observed in COVID‐19 patients (median 0.35%), and three‐time vaccinees showed a higher magnitude than two‐time vaccinees (median 0.091% vs. 0.175%, P < 0.0001). Twelve peptide specificities were each detected in at least 40% of subjects. In vitro HLA binding showed promiscuous presentation by DRB1 molecules for several peptides. Conclusion Both SARS‐CoV‐2 infection and vaccination prime broadly directed T‐cell responses directed against the SARS‐CoV‐2 spike glycoprotein. This comprehensive high‐resolution analysis of spike peptide specificities will be a useful resource for further investigation of spike‐specific T‐cell responses. Individual CD4+ and CD8+ T‐cell responses directed against a total of 253 overlapping 15‐mer spike‐specific peptides were mapped in a cohort of COVID‐19 patients (n = 8), uninfected vaccinees (n = 16) and individuals who experienced both infection and vaccination (n = 11). We found that patients and vaccinees (two‐time and three‐time vaccinees alike) had a comparable number of CD4+ T‐cell responses (median 26 vs. 29, P = 0.7289) but differential magnitudes of these in vitro responses (median 0.35% vs. 0.12% IFN‐γ+ of CD4+ T cells, P < 0.0001). Most of the recognized specificities were conserved in the B.1.1.529 (omicron) Variant of Concern (VoC), and its sublineages and several peptides showed promiscuous presentation by DRB1 molecules in in vitro HLA‐binding assays.
Potential differences in the breadth, distribution and magnitude of CD4 T-cell responses directed against the SARS-CoV-2 spike glycoprotein between vaccinees, COVID-19 patients and subjects who experienced both ways of immunisation have not been comprehensively compared on a peptide level. Following virus-specific cultivation, we determined the T-cell responses directed against 253 individual overlapping 15-mer peptides covering the entire SARS-CoV-2 spike glycoprotein using IFN-γ ELISpot and intracellular cytokine staining. HLA binding was determined for selected peptides. We mapped 955 single peptide-specific CD4 T-cell responses in a cohort of COVID-19 patients (  = 8), uninfected vaccinees (  = 16) and individuals who experienced both infection and vaccination (  = 11). Patients and vaccinees (two-time and three-time vaccinees alike) had a comparable number of CD4 T-cell responses (median 26 vs. 29,  = 0.7289). Most of these specificities were conserved in B.1.1.529 and the BA.4 and BA.5 sublineages. The highest magnitude of these IFN-γ CD4 T-cell responses was observed in COVID-19 patients (median 0.35%), and three-time vaccinees showed a higher magnitude than two-time vaccinees (median 0.091% vs. 0.175%,  < 0.0001). Twelve peptide specificities were each detected in at least 40% of subjects. HLA binding showed promiscuous presentation by DRB1 molecules for several peptides. Both SARS-CoV-2 infection and vaccination prime broadly directed T-cell responses directed against the SARS-CoV-2 spike glycoprotein. This comprehensive high-resolution analysis of spike peptide specificities will be a useful resource for further investigation of spike-specific T-cell responses.
Individual CD4 + and CD8 + T‐cell responses directed against a total of 253 overlapping 15‐mer spike‐specific peptides were mapped in a cohort of COVID‐19 patients ( n  = 8), uninfected vaccinees ( n  = 16) and individuals who experienced both infection and vaccination ( n  = 11). We found that patients and vaccinees (two‐time and three‐time vaccinees alike) had a comparable number of CD4 + T‐cell responses (median 26 vs. 29, P  = 0.7289) but differential magnitudes of these in vitro responses (median 0.35% vs. 0.12% IFN‐γ + of CD4 + T cells, P  < 0.0001). Most of the recognized specificities were conserved in the B.1.1.529 (omicron) Variant of Concern (VoC), and its sublineages and several peptides showed promiscuous presentation by DRB1 molecules in in vitro HLA‐binding assays.
Potential differences in the breadth, distribution and magnitude of CD4+ T-cell responses directed against the SARS-CoV-2 spike glycoprotein between vaccinees, COVID-19 patients and subjects who experienced both ways of immunisation have not been comprehensively compared on a peptide level.ObjectivesPotential differences in the breadth, distribution and magnitude of CD4+ T-cell responses directed against the SARS-CoV-2 spike glycoprotein between vaccinees, COVID-19 patients and subjects who experienced both ways of immunisation have not been comprehensively compared on a peptide level.Following virus-specific in vitro cultivation, we determined the T-cell responses directed against 253 individual overlapping 15-mer peptides covering the entire SARS-CoV-2 spike glycoprotein using IFN-γ ELISpot and intracellular cytokine staining. In vitro HLA binding was determined for selected peptides.MethodsFollowing virus-specific in vitro cultivation, we determined the T-cell responses directed against 253 individual overlapping 15-mer peptides covering the entire SARS-CoV-2 spike glycoprotein using IFN-γ ELISpot and intracellular cytokine staining. In vitro HLA binding was determined for selected peptides.We mapped 955 single peptide-specific CD4+ T-cell responses in a cohort of COVID-19 patients (n = 8), uninfected vaccinees (n = 16) and individuals who experienced both infection and vaccination (n = 11). Patients and vaccinees (two-time and three-time vaccinees alike) had a comparable number of CD4+ T-cell responses (median 26 vs. 29, P = 0.7289). Most of these specificities were conserved in B.1.1.529 and the BA.4 and BA.5 sublineages. The highest magnitude of these in vitro IFN-γ CD4+ T-cell responses was observed in COVID-19 patients (median 0.35%), and three-time vaccinees showed a higher magnitude than two-time vaccinees (median 0.091% vs. 0.175%, P < 0.0001). Twelve peptide specificities were each detected in at least 40% of subjects. In vitro HLA binding showed promiscuous presentation by DRB1 molecules for several peptides.ResultsWe mapped 955 single peptide-specific CD4+ T-cell responses in a cohort of COVID-19 patients (n = 8), uninfected vaccinees (n = 16) and individuals who experienced both infection and vaccination (n = 11). Patients and vaccinees (two-time and three-time vaccinees alike) had a comparable number of CD4+ T-cell responses (median 26 vs. 29, P = 0.7289). Most of these specificities were conserved in B.1.1.529 and the BA.4 and BA.5 sublineages. The highest magnitude of these in vitro IFN-γ CD4+ T-cell responses was observed in COVID-19 patients (median 0.35%), and three-time vaccinees showed a higher magnitude than two-time vaccinees (median 0.091% vs. 0.175%, P < 0.0001). Twelve peptide specificities were each detected in at least 40% of subjects. In vitro HLA binding showed promiscuous presentation by DRB1 molecules for several peptides.Both SARS-CoV-2 infection and vaccination prime broadly directed T-cell responses directed against the SARS-CoV-2 spike glycoprotein. This comprehensive high-resolution analysis of spike peptide specificities will be a useful resource for further investigation of spike-specific T-cell responses.ConclusionBoth SARS-CoV-2 infection and vaccination prime broadly directed T-cell responses directed against the SARS-CoV-2 spike glycoprotein. This comprehensive high-resolution analysis of spike peptide specificities will be a useful resource for further investigation of spike-specific T-cell responses.
ObjectivesPotential differences in the breadth, distribution and magnitude of CD4+ T‐cell responses directed against the SARS‐CoV‐2 spike glycoprotein between vaccinees, COVID‐19 patients and subjects who experienced both ways of immunisation have not been comprehensively compared on a peptide level.MethodsFollowing virus‐specific in vitro cultivation, we determined the T‐cell responses directed against 253 individual overlapping 15‐mer peptides covering the entire SARS‐CoV‐2 spike glycoprotein using IFN‐γ ELISpot and intracellular cytokine staining. In vitro HLA binding was determined for selected peptides.ResultsWe mapped 955 single peptide‐specific CD4+ T‐cell responses in a cohort of COVID‐19 patients (n = 8), uninfected vaccinees (n = 16) and individuals who experienced both infection and vaccination (n = 11). Patients and vaccinees (two‐time and three‐time vaccinees alike) had a comparable number of CD4+ T‐cell responses (median 26 vs. 29, P = 0.7289). Most of these specificities were conserved in B.1.1.529 and the BA.4 and BA.5 sublineages. The highest magnitude of these in vitro IFN‐γ CD4+ T‐cell responses was observed in COVID‐19 patients (median 0.35%), and three‐time vaccinees showed a higher magnitude than two‐time vaccinees (median 0.091% vs. 0.175%, P < 0.0001). Twelve peptide specificities were each detected in at least 40% of subjects. In vitro HLA binding showed promiscuous presentation by DRB1 molecules for several peptides.ConclusionBoth SARS‐CoV‐2 infection and vaccination prime broadly directed T‐cell responses directed against the SARS‐CoV‐2 spike glycoprotein. This comprehensive high‐resolution analysis of spike peptide specificities will be a useful resource for further investigation of spike‐specific T‐cell responses.
Abstract Objectives Potential differences in the breadth, distribution and magnitude of CD4+ T‐cell responses directed against the SARS‐CoV‐2 spike glycoprotein between vaccinees, COVID‐19 patients and subjects who experienced both ways of immunisation have not been comprehensively compared on a peptide level. Methods Following virus‐specific in vitro cultivation, we determined the T‐cell responses directed against 253 individual overlapping 15‐mer peptides covering the entire SARS‐CoV‐2 spike glycoprotein using IFN‐γ ELISpot and intracellular cytokine staining. In vitro HLA binding was determined for selected peptides. Results We mapped 955 single peptide‐specific CD4+ T‐cell responses in a cohort of COVID‐19 patients (n = 8), uninfected vaccinees (n = 16) and individuals who experienced both infection and vaccination (n = 11). Patients and vaccinees (two‐time and three‐time vaccinees alike) had a comparable number of CD4+ T‐cell responses (median 26 vs. 29, P = 0.7289). Most of these specificities were conserved in B.1.1.529 and the BA.4 and BA.5 sublineages. The highest magnitude of these in vitro IFN‐γ CD4+ T‐cell responses was observed in COVID‐19 patients (median 0.35%), and three‐time vaccinees showed a higher magnitude than two‐time vaccinees (median 0.091% vs. 0.175%, P < 0.0001). Twelve peptide specificities were each detected in at least 40% of subjects. In vitro HLA binding showed promiscuous presentation by DRB1 molecules for several peptides. Conclusion Both SARS‐CoV‐2 infection and vaccination prime broadly directed T‐cell responses directed against the SARS‐CoV‐2 spike glycoprotein. This comprehensive high‐resolution analysis of spike peptide specificities will be a useful resource for further investigation of spike‐specific T‐cell responses.
Author Karsten, Hendrik
Schmiedel, Stefan
Huber, Samuel
Schulze zur Wiesch, Julian
Brehm, Thomas Theo
Ackermann, Christin
Cords, Leon
Sette, Alessandro
Addo, Marylyn Martina
Ditt, Vanessa
Sidney, John
Peine, Sven
Knapp, Maximilian
Lütgehetmann, Marc
Wittner, Melanie
Woost, Robin
Omansen, Till Frederik
Westphal, Tim
Hermanussen, Lennart
AuthorAffiliation 1 Infectious Diseases Unit, 1. Department of Medicine University Medical Center Hamburg‐Eppendorf Hamburg Germany
3 Department of Tropical Medicine Bernhard Nocht Institute for Tropical Medicine Hamburg Germany
4 Institute of Transfusion Medicine University Medical Center Hamburg‐Eppendorf Hamburg Germany
5 Institute of Medical Microbiology, Virology and Hygiene University Medical Center Hamburg‐Eppendorf Hamburg Germany
6 Center for Infectious Disease and Vaccine Research La Jolla Institute for Immunology (LJI) La Jolla CA USA
2 German Center for Infection Research (DZIF) Partner Site Hamburg‐Lübeck‐Borstel‐Riems Hamburg Germany
AuthorAffiliation_xml – name: 3 Department of Tropical Medicine Bernhard Nocht Institute for Tropical Medicine Hamburg Germany
– name: 4 Institute of Transfusion Medicine University Medical Center Hamburg‐Eppendorf Hamburg Germany
– name: 1 Infectious Diseases Unit, 1. Department of Medicine University Medical Center Hamburg‐Eppendorf Hamburg Germany
– name: 5 Institute of Medical Microbiology, Virology and Hygiene University Medical Center Hamburg‐Eppendorf Hamburg Germany
– name: 2 German Center for Infection Research (DZIF) Partner Site Hamburg‐Lübeck‐Borstel‐Riems Hamburg Germany
– name: 6 Center for Infectious Disease and Vaccine Research La Jolla Institute for Immunology (LJI) La Jolla CA USA
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  organization: University Medical Center Hamburg‐Eppendorf
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/35957961$$D View this record in MEDLINE/PubMed
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Copyright 2022 The Authors. published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.
2022 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.
2022. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
Copyright_xml – notice: 2022 The Authors. published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.
– notice: 2022 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.
– notice: 2022. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
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Keywords CD4+ T cells
MHC class II
B.1.1.529
SARS‐CoV‐2
vaccines
spike protein
Language English
License Attribution
2022 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.
This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
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Snippet Objectives Potential differences in the breadth, distribution and magnitude of CD4+ T‐cell responses directed against the SARS‐CoV‐2 spike glycoprotein between...
Potential differences in the breadth, distribution and magnitude of CD4 T-cell responses directed against the SARS-CoV-2 spike glycoprotein between vaccinees,...
ObjectivesPotential differences in the breadth, distribution and magnitude of CD4+ T‐cell responses directed against the SARS‐CoV‐2 spike glycoprotein between...
Potential differences in the breadth, distribution and magnitude of CD4+ T-cell responses directed against the SARS-CoV-2 spike glycoprotein between vaccinees,...
Individual CD4 + and CD8 + T‐cell responses directed against a total of 253 overlapping 15‐mer spike‐specific peptides were mapped in a cohort of COVID‐19...
Abstract Objectives Potential differences in the breadth, distribution and magnitude of CD4+ T‐cell responses directed against the SARS‐CoV‐2 spike...
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pubmedcentral
proquest
pubmed
crossref
wiley
SourceType Open Website
Open Access Repository
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Publisher
StartPage e1410
SubjectTerms Antibodies
B.1.1.529
CD4 antigen
CD4+ T cells
Coronaviruses
COVID-19
COVID-19 vaccines
Cytokines
Drb1 protein
Enzyme-linked immunosorbent assay
Glycoproteins
Histocompatibility antigen HLA
Infections
Interferon
Lymphocytes
MHC class II
Original
Patients
Peptides
SARS‐CoV‐2
Severe acute respiratory syndrome coronavirus 2
Spike glycoprotein
spike protein
Vaccination
vaccines
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Title High‐resolution analysis of individual spike peptide‐specific CD4+ T‐cell responses in vaccine recipients and COVID‐19 patients
URI https://onlinelibrary.wiley.com/doi/abs/10.1002%2Fcti2.1410
https://www.ncbi.nlm.nih.gov/pubmed/35957961
https://www.proquest.com/docview/2707499261
https://www.proquest.com/docview/2702181506
https://pubmed.ncbi.nlm.nih.gov/PMC9363231
https://doaj.org/article/0f54419279204946b17ccd56963a3483
Volume 11
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