TY  - JOUR
AB  - 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.
AU  - Huber, J.E.*
AU  - Ahlfeld, J.
AU  - Scheck, M.K.*
AU  - Zaucha, M.*
AU  - Witter, K.*
AU  - Lehmann, L.*
AU  - Karimzadeh, H.
AU  - Pritsch, M.*
AU  - Hoelscher, M.*
AU  - von Sonnenburg, F.*
AU  - Dick, A.*
AU  - Barba-Spaeth, G.*
AU  - Krug, A.B.*
AU  - Rothenfußer, S.
AU  - Baumjohann, D.*
C1  - 59147
C2  - 48599
CY  - 111 River St, Hoboken 07030-5774, Nj Usa
TI  - Dynamic changes in circulating T follicular helper cell composition predict neutralising antibody responses after yellow fever vaccination.
JO  - Clin. Transl. Immunology
VL  - 9
IS  - 5
PB  - Wiley
PY  - 2020
SN  - 2050-0068
ER  - 

TY  - JOUR
AB  - Objectives Innovative post-remission therapies are needed to eliminate residual AML cells. DC vaccination is a promising strategy to induce anti-leukaemic immune responses.Methods We conducted a first-in-human phase I study using TLR7/8-matured DCs transfected with RNA encoding the two AML-associated antigens WT1 and PRAME as well as CMVpp65. AML patients in CR at high risk of relapse were vaccinated 10x over 26 weeks.Results Despite heavy pretreatment, DCs of sufficient number and quality were generated from a single leukapheresis in 11/12 cases, and 10 patients were vaccinated. Administration was safe and resulted in local inflammatory responses with dense T-cell infiltration. In peripheral blood, increased antigen-specific CD8(+) T cells were seen for WT1 (2/10), PRAME (4/10) and CMVpp65 (9/10). For CMVpp65, increased CD4(+) T cells were detected in 4/7 patients, and an antibody response was induced in 3/7 initially seronegative patients. Median OS was not reached after 1057 days; median RFS was 1084 days. A positive correlation was observed between clinical benefit and younger age as well as mounting of antigen-specific immune responses.Conclusions Administration of TLR7/8-matured DCs to AML patients in CR at high risk of relapse was feasible and safe and resulted in induction of antigen-specific immune responses. Clinical benefit appeared to occur more likely in patients The study was registered at on 17 October 2012 (NCT01734304) and at (EudraCT-Number 2010-022446-24) on 10 October 2013.
AU  - Lichtenegger, F.S.*
AU  - Schnorfeil, F.M.*
AU  - Rothe, M.*
AU  - Deiser, K.*
AU  - Altmann, T.*
AU  - Bücklein, V.L.*
AU  - Köhnke, T.*
AU  - Augsberger, C.*
AU  - Konstandin, N.P.*
AU  - Spiekermann, K.*
AU  - Moosmann, A.
AU  - Boehm, S.*
AU  - Boxberg, M.*
AU  - Heemskerk, M.H.M.*
AU  - Goerlich, D.*
AU  - Wittmann, G.*
AU  - Wagner, B.*
AU  - Hiddemann, W.*
AU  - Schendel, D.J.*
AU  - Kvalheim, G.*
AU  - Bigalke, I.*
AU  - Subklewe, M.*
C1  - 58752
C2  - 48378
CY  - 111 River St, Hoboken 07030-5774, Nj Usa
TI  - Toll-like receptor 7/8-matured RNA-transduced dendritic cells as post-remission therapy in acute myeloid leukaemia: Results of a phase I trial.
JO  - Clin. Transl. Immunology
VL  - 9
IS  - 3
PB  - Wiley
PY  - 2020
SN  - 2050-0068
ER  -