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

循环 T 滤泡辅助细胞组成的动态变化可预测黄热病疫苗接种后的中和抗体反应

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作者: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

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.

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.

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