Huber, J.E.* ; Ahlfeld, J. ; Scheck, M.K.* ; Zaucha, M.* ; Witter, K.* ; Lehmann, L.* ; Karimzadeh, H. ; Pritsch, M.* ; Hoelscher, M.* ; von Sonnenburg, F.* ; Dick, A.* ; Barba-Spaeth, G.* ; Krug, A.B.* ; Rothenfußer, S. ; Baumjohann, D.*
Dynamic changes in circulating T follicular helper cell composition predict neutralising antibody responses after yellow fever vaccination.
Clin. Transl. Immunology 9:e1129 (2020)
Objectives T follicular helper (Tfh) cells are the principal T helper cell subset that provides help to B cells for potent antibody responses against various pathogens. In this study, we took advantage of the live-attenuated yellow fever virus (YFV) vaccine strain, YF-17D, as a model system for studying human antiviral immune responses in vivo following exposure to an acute primary virus challenge under safe and highly controlled conditions, to comprehensively analyse the dynamics of circulating Tfh (cTfh) cells.Methods We tracked and analysed the response of cTfh and other T and B cell subsets in peripheral blood of healthy volunteers by flow cytometry over the course of 4 weeks after YF-17D vaccination.Results Using surface staining of cell activation markers to track YFV-specific T cells, we found increasing cTfh cell frequencies starting at day 3 and peaking around 2 weeks after YF-17D vaccination. This kinetic was confirmed in a subgroup of donors using MHC multimer staining for four known MHC class II epitopes of YF-17D. The subset composition of cTfh cells changed dynamically during the course of the immune response and was dominated by the cTfh1-polarised subpopulation. Importantly, frequencies of cTfh1 cells correlated with the strength of the neutralising antibody response, whereas frequencies of cTfh17 cells were inversely correlated.Conclusion In summary, we describe detailed cTfh kinetics during YF-17D vaccination. Our results suggest that cTfh expansion and polarisation can serve as a prognostic marker for vaccine success. These insights may be leveraged in the future to improve current vaccine design and strategies.
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Publication type
Article: Journal article
Document type
Scientific Article
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Keywords
Neutralising Antibodies ; T Follicular Helper (tfh) Cells ; Vaccination ; Viral Infection ; Yellow Fever ; Yf-17d; Virus 17d; Effector; Immunity; Biology; Blood
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Language
english
Publication Year
2020
Prepublished in Year
HGF-reported in Year
2020
ISSN (print) / ISBN
2050-0068
e-ISSN
2050-0068
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Volume: 9,
Issue: 5,
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Article Number: e1129
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Nature Publishing Group
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London
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Peer reviewed
POF-Topic(s)
30203 - Molecular Targets and Therapies
Research field(s)
Immune Response and Infection
PSP Element(s)
G-522100-001
G-502700-003
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Erfassungsdatum
2020-05-20