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

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 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 ª prognostic marker for vaccine success. These insights may be leveraged in the future to improve current vaccine design and strategies.

Integrated immune dynamics define correlates of COVID-19 severity and antibody responses

“…Our data are in agreement with the emergence of IgG, IgM, and IgA ASC in COVID-19 patients, some specific for non-Spike antigens (e.g., nucleocapsid protein), which may explain the lack of a strong correlation between ASCs and RBD-specific antibodies in our cohort and other studies. 4,6 Activation of cT FH 1 cells is an important correlate of antibody responses following influenza vaccination, 25 yellow fever, 33 and hepatitis C virus (HCV). 34 Although the lack of Bcl6 + T FH cells in lymphoid organs of severely ill COVID-19 patients was shown, 35 cT FH response at the convalescent phase was associated with antibody responses to SARS-CoV-2.…”

Immunogenicity of prime-boost protein subunit vaccine strategies against SARS-CoV-2 in mice and macaques

“…3J). Among all animals, RBDspecific cTFH frequencies correlated with S antibody titres suggesting that, analogous to humans [24][25][26][27][28] , antigen-specific cTFH constitute a useful biomarker of vaccine immunogenicity in NHP models (p = 0.04, Fig. S13C).…”

Prime-boost protein subunit vaccines against SARS-CoV-2 are highly immunogenic in mice and macaques

“…In contrast to previous observations in convalescent human donors (Juno), NHP S-specific cTFH recognised non-RBD and RBD-derived peptides at similar frequencies ( Figure 3J). Among all animals, RBD-specific cTFH frequencies correlated with S antibody titres suggesting that, analagous to humans (Bentebibel et al, 2013(Bentebibel et al, , 2016Farooq et al, 2016;Huber et al, 2020;Koutsakos et al, 2018), antigen-specific cTFH constitute a useful biomarker of vaccine immunogenicity in NHP models (p=0.04, Figure S9D).…”