Abstract
ObjectivesT 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.MethodsWe 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.ResultsUsing 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.ConclusionIn 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.
Highlights
Emerging new viral infections and re-emerging known viral pathogens are posing an ever-growing threat, especially if preventive measures in form of vaccinations are not available or limited
YF-17D vaccination lead to a characteristic transient decrease in the absolute cell numbers of CD8+ cells on day 3 and day 7 after vaccination and a significant increase in the frequency of CD38-expressing activated CD8+ T cells from day 3 on, peaking on day 14 (Supplementary figure 2a and b), which is in line with previous reports.[21,22]
While none of the frequencies of CXCR5À cTmem cells as well as none of the prevaccination (0 dpv) frequencies of circulating Tfh (cTfh) cell parameters correlated with the neutralising antibody titre, we found that the frequencies of cTfh[1] and cTfh[17] cells correlated with the neutralising activity measured in the serum of vaccines (Figure 7a and b). cTfh[1] cell frequencies on day 14 and day 28 correlated positively with the measured neutralising activity a 2020 The Authors
Summary
Emerging new viral infections and re-emerging known viral pathogens are posing an ever-growing threat, especially if preventive measures in form of vaccinations are not available or limited. A solid understanding of the cellular immune response to viral infection is of immense importance for the development of new vaccines and antiviral treatments. The liveattenuated YFV strain 17D has been developed and used since the 1930s,2 leading to livelong immunity in over 98% of vaccinees after a single shot.[3] This efficiency relies on the generation of neutralising antibodies as well as on the formation of CD4+ T cell memory.[4,5,6] Neutralising antibodies are detected starting 10 days post-vaccination and can persist for decades after immunisation.[7] Adverse events of the vaccination are extremely rare, which makes the vaccination with YF-17D a safe and beneficial intervention that can be used to model an acute viral infection to study innate and adaptive antiviral immune responses in human subjects
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
