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Clin Transl Immunology. 2020 May 13;9(5):e1129. doi: 10.1002/cti2.1129. eCollection 2020 May.

Dynamic changes in circulating T follicular helper cell composition predict neutralising antibody responses after yellow fever vaccination.

Clinical & translational immunology

Johanna E Huber, Julia Ahlfeld, Magdalena K Scheck, Magdalena Zaucha, Klaus Witter, Lisa Lehmann, Hadi Karimzadeh, Michael Pritsch, Michael Hoelscher, Frank von Sonnenburg, Andrea Dick, Giovanna Barba-Spaeth, Anne B Krug, Simon Rothenfußer, Dirk Baumjohann

Affiliations

  1. Institute for Immunology Biomedical Center Faculty of Medicine LMU Munich Planegg-Martinsried Germany.
  2. Division of Clinical Pharmacology University Hospital LMU Munich Munich Germany.
  3. Einheit für Klinische Pharmakologie (EKLiP) Helmholtz Zentrum München German Research Center for Environmental Health (HMGU) Neuherberg Germany.
  4. Present address: Department of Pharmacy LMU Munich Munich Germany.
  5. Laboratory of Immunogenetics and Molecular Diagnostics Department of Transfusion Medicine, Cell Therapeutic Agents and Hemostaseology LMU Munich Munich Germany.
  6. Division of Infectious Diseases and Tropical Medicine University Hospital LMU Munich Munich Germany.
  7. German Center for Infection Research, partner site Munich Munich Germany.
  8. Structural Virology Unit and CNRS UMR 3569 Virology Department Institut Pasteur Paris France.
  9. Medical Clinic III for Oncology, Hematology, Immuno-Oncology and Rheumatology University Hospital Bonn University of Bonn Bonn Germany.

PMID: 32419947 PMCID: PMC7221214 DOI: 10.1002/cti2.1129

Abstract

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

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.

© 2020 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.

Keywords: T follicular helper (Tfh) cells; YF‐17D; neutralising antibodies; vaccination; viral infection; yellow fever

Conflict of interest statement

The authors declare no conflict of interest.

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