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 journal › SCORING: Journal article › Research › peer-review
Harvard
APA
Vancouver
Bibtex
}
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 -