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

Standard

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

In: CLIN TRANSL IMMUNOL, Vol. 11, No. 8, e1410, 2022.

Research output: SCORING: Contribution to journalSCORING: Journal articleResearchpeer-review

Harvard

APA

Vancouver

Bibtex

@article{92953303eabf4e98a33600d949738a84,
title = "High-resolution analysis of individual spike peptide-specific CD4+ T-cell responses in vaccine recipients and COVID-19 patients",
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 = "Hendrik Karsten and Leon Cords and Tim Westphal and Maximilian Knapp and Brehm, {Thomas Theo} and Lennart Hermanussen and Omansen, {Till Frederik} and Stefan Schmiedel and Robin Woost and Vanessa Ditt and Sven Peine and Marc L{\"u}tgehetmann and Samuel Huber and Christin Ackermann and Melanie Wittner and Addo, {Marylyn Martina} and Alessandro Sette and John Sidney and {Schulze Zur Wiesch}, Julian",
note = "{\textcopyright} 2022 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.",
year = "2022",
doi = "10.1002/cti2.1410",
language = "English",
volume = "11",
journal = "CLIN TRANSL IMMUNOL",
issn = "2050-0068",
publisher = "John Wiley & Sons Inc.",
number = "8",

}

RIS

TY - JOUR

T1 - High-resolution analysis of individual spike peptide-specific CD4+ T-cell responses in vaccine recipients and COVID-19 patients

AU - Karsten, Hendrik

AU - Cords, Leon

AU - Westphal, Tim

AU - Knapp, Maximilian

AU - Brehm, Thomas Theo

AU - Hermanussen, Lennart

AU - Omansen, Till Frederik

AU - Schmiedel, Stefan

AU - Woost, Robin

AU - Ditt, Vanessa

AU - Peine, Sven

AU - Lütgehetmann, Marc

AU - Huber, Samuel

AU - Ackermann, Christin

AU - Wittner, Melanie

AU - Addo, Marylyn Martina

AU - Sette, Alessandro

AU - Sidney, John

AU - Schulze Zur Wiesch, Julian

N1 - © 2022 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.

PY - 2022

Y1 - 2022

N2 - 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.

AB - 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.

U2 - 10.1002/cti2.1410

DO - 10.1002/cti2.1410

M3 - SCORING: Journal article

C2 - 35957961

VL - 11

JO - CLIN TRANSL IMMUNOL

JF - CLIN TRANSL IMMUNOL

SN - 2050-0068

IS - 8

M1 - e1410

ER -