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A new synthetic toll-like receptor 1/2 ligand is an efficient adjuvant for peptide vaccination in a human volunteer

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A new synthetic toll-like receptor 1/2 ligand is an efficient adjuvant for peptide vaccination in a human volunteer. / Rammensee, Hans-Georg; Wiesmüller, Karl-Heinz; Chandran, P Anoop; Zelba, Henning; Rusch, Elisa; Gouttefangeas, Cécile; Kowalewski, Daniel J; Di Marco, Moreno; Haen, Sebastian P; Walz, Juliane S; Gloria, Yamel Cardona; Bödder, Johanna; Schertel, Jill-Marie; Tunger, Antje; Müller, Luise; Kießler, Maximilian; Wehner, Rebekka; Schmitz, Marc; Jakobi, Meike; Schneiderhan-Marra, Nicole; Klein, Reinhild; Laske, Karoline; Artzner, Kerstin; Backert, Linus; Schuster, Heiko; Schwenck, Johannes; Weber, Alexander N R; Pichler, Bernd J; Kneilling, Manfred; la Fougère, Christian; Forchhammer, Stephan; Metzler, Gisela; Bauer, Jürgen; Weide, Benjamin; Schippert, Wilfried; Stevanović, Stefan; Löffler, Markus W.

in: J IMMUNOTHER CANCER, Jahrgang 7, Nr. 1, 15.11.2019, S. 307.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Rammensee, H-G, Wiesmüller, K-H, Chandran, PA, Zelba, H, Rusch, E, Gouttefangeas, C, Kowalewski, DJ, Di Marco, M, Haen, SP, Walz, JS, Gloria, YC, Bödder, J, Schertel, J-M, Tunger, A, Müller, L, Kießler, M, Wehner, R, Schmitz, M, Jakobi, M, Schneiderhan-Marra, N, Klein, R, Laske, K, Artzner, K, Backert, L, Schuster, H, Schwenck, J, Weber, ANR, Pichler, BJ, Kneilling, M, la Fougère, C, Forchhammer, S, Metzler, G, Bauer, J, Weide, B, Schippert, W, Stevanović, S & Löffler, MW 2019, 'A new synthetic toll-like receptor 1/2 ligand is an efficient adjuvant for peptide vaccination in a human volunteer', J IMMUNOTHER CANCER, Jg. 7, Nr. 1, S. 307. https://doi.org/10.1186/s40425-019-0796-5

APA

Rammensee, H-G., Wiesmüller, K-H., Chandran, P. A., Zelba, H., Rusch, E., Gouttefangeas, C., Kowalewski, D. J., Di Marco, M., Haen, S. P., Walz, J. S., Gloria, Y. C., Bödder, J., Schertel, J-M., Tunger, A., Müller, L., Kießler, M., Wehner, R., Schmitz, M., Jakobi, M., ... Löffler, M. W. (2019). A new synthetic toll-like receptor 1/2 ligand is an efficient adjuvant for peptide vaccination in a human volunteer. J IMMUNOTHER CANCER, 7(1), 307. https://doi.org/10.1186/s40425-019-0796-5

Vancouver

Rammensee H-G, Wiesmüller K-H, Chandran PA, Zelba H, Rusch E, Gouttefangeas C et al. A new synthetic toll-like receptor 1/2 ligand is an efficient adjuvant for peptide vaccination in a human volunteer. J IMMUNOTHER CANCER. 2019 Nov 15;7(1):307. https://doi.org/10.1186/s40425-019-0796-5

Bibtex

@article{37e70edf057c426c971921f171134df5,
title = "A new synthetic toll-like receptor 1/2 ligand is an efficient adjuvant for peptide vaccination in a human volunteer",
abstract = "BACKGROUND: We previously showed that the bacterial lipopeptide Pam3Cys-Ser-Ser, meanwhile established as a toll-like receptor (TLR) 1/2 ligand, acts as a strong adjuvant for the induction of virus specific CD8+ T cells in mice, when covalently coupled to a synthetic peptide.CASE PRESENTATION: We now designed a new water-soluble synthetic Pam3Cys-derivative, named XS15 and characterized it in vitro by a TLR2 NF-κB luciferase reporter assay. Further, the capacity of XS15 to activate immune cells and stimulate peptide-specific CD8+ T and NK cells by 6-sulfo LacNAc+ monocytes was assessed by flow cytometry as well as cytokine induction using immunoassays. The induction of a functional immune response after vaccination of a volunteer with viral peptides was assessed by ELISpot assay and flow cytometry in peripheral blood cells and infiltrating cells at the vaccination site, as well as by immunohistochemistry and imaging. XS15 induced strong ex vivo CD8+ and TH1 CD4+ responses in a human volunteer upon a single injection of XS15 mixed to uncoupled peptides in a water-in-oil emulsion (Montanide{\texttrademark} ISA51 VG). A granuloma formed locally at the injection site containing highly activated functional CD4+ and CD8+ effector memory T cells. The total number of vaccine peptide-specific functional T cells was experimentally assessed and estimated to be 3.0 × 105 in the granuloma and 20.5 × 106 in peripheral blood.CONCLUSION: Thus, in one volunteer we show a granuloma forming by peptides combined with an efficient adjuvant in a water-in-oil-emulsion, inducing antigen specific T cells detectable in circulation and at the vaccination site, after one single vaccination only. The ex vivo T cell responses in peripheral blood were detectable for more than one year and could be strongly boosted by a second vaccination. Hence, XS15 is a promising adjuvant candidate for peptide vaccination, in particular for tumor peptide vaccines in a personalized setting.",
author = "Hans-Georg Rammensee and Karl-Heinz Wiesm{\"u}ller and Chandran, {P Anoop} and Henning Zelba and Elisa Rusch and C{\'e}cile Gouttefangeas and Kowalewski, {Daniel J} and {Di Marco}, Moreno and Haen, {Sebastian P} and Walz, {Juliane S} and Gloria, {Yamel Cardona} and Johanna B{\"o}dder and Jill-Marie Schertel and Antje Tunger and Luise M{\"u}ller and Maximilian Kie{\ss}ler and Rebekka Wehner and Marc Schmitz and Meike Jakobi and Nicole Schneiderhan-Marra and Reinhild Klein and Karoline Laske and Kerstin Artzner and Linus Backert and Heiko Schuster and Johannes Schwenck and Weber, {Alexander N R} and Pichler, {Bernd J} and Manfred Kneilling and {la Foug{\`e}re}, Christian and Stephan Forchhammer and Gisela Metzler and J{\"u}rgen Bauer and Benjamin Weide and Wilfried Schippert and Stefan Stevanovi{\'c} and L{\"o}ffler, {Markus W}",
year = "2019",
month = nov,
day = "15",
doi = "10.1186/s40425-019-0796-5",
language = "English",
volume = "7",
pages = "307",
journal = "J IMMUNOTHER CANCER",
issn = "2051-1426",
publisher = "BioMed Central Ltd.",
number = "1",

}

RIS

TY - JOUR

T1 - A new synthetic toll-like receptor 1/2 ligand is an efficient adjuvant for peptide vaccination in a human volunteer

AU - Rammensee, Hans-Georg

AU - Wiesmüller, Karl-Heinz

AU - Chandran, P Anoop

AU - Zelba, Henning

AU - Rusch, Elisa

AU - Gouttefangeas, Cécile

AU - Kowalewski, Daniel J

AU - Di Marco, Moreno

AU - Haen, Sebastian P

AU - Walz, Juliane S

AU - Gloria, Yamel Cardona

AU - Bödder, Johanna

AU - Schertel, Jill-Marie

AU - Tunger, Antje

AU - Müller, Luise

AU - Kießler, Maximilian

AU - Wehner, Rebekka

AU - Schmitz, Marc

AU - Jakobi, Meike

AU - Schneiderhan-Marra, Nicole

AU - Klein, Reinhild

AU - Laske, Karoline

AU - Artzner, Kerstin

AU - Backert, Linus

AU - Schuster, Heiko

AU - Schwenck, Johannes

AU - Weber, Alexander N R

AU - Pichler, Bernd J

AU - Kneilling, Manfred

AU - la Fougère, Christian

AU - Forchhammer, Stephan

AU - Metzler, Gisela

AU - Bauer, Jürgen

AU - Weide, Benjamin

AU - Schippert, Wilfried

AU - Stevanović, Stefan

AU - Löffler, Markus W

PY - 2019/11/15

Y1 - 2019/11/15

N2 - BACKGROUND: We previously showed that the bacterial lipopeptide Pam3Cys-Ser-Ser, meanwhile established as a toll-like receptor (TLR) 1/2 ligand, acts as a strong adjuvant for the induction of virus specific CD8+ T cells in mice, when covalently coupled to a synthetic peptide.CASE PRESENTATION: We now designed a new water-soluble synthetic Pam3Cys-derivative, named XS15 and characterized it in vitro by a TLR2 NF-κB luciferase reporter assay. Further, the capacity of XS15 to activate immune cells and stimulate peptide-specific CD8+ T and NK cells by 6-sulfo LacNAc+ monocytes was assessed by flow cytometry as well as cytokine induction using immunoassays. The induction of a functional immune response after vaccination of a volunteer with viral peptides was assessed by ELISpot assay and flow cytometry in peripheral blood cells and infiltrating cells at the vaccination site, as well as by immunohistochemistry and imaging. XS15 induced strong ex vivo CD8+ and TH1 CD4+ responses in a human volunteer upon a single injection of XS15 mixed to uncoupled peptides in a water-in-oil emulsion (Montanide™ ISA51 VG). A granuloma formed locally at the injection site containing highly activated functional CD4+ and CD8+ effector memory T cells. The total number of vaccine peptide-specific functional T cells was experimentally assessed and estimated to be 3.0 × 105 in the granuloma and 20.5 × 106 in peripheral blood.CONCLUSION: Thus, in one volunteer we show a granuloma forming by peptides combined with an efficient adjuvant in a water-in-oil-emulsion, inducing antigen specific T cells detectable in circulation and at the vaccination site, after one single vaccination only. The ex vivo T cell responses in peripheral blood were detectable for more than one year and could be strongly boosted by a second vaccination. Hence, XS15 is a promising adjuvant candidate for peptide vaccination, in particular for tumor peptide vaccines in a personalized setting.

AB - BACKGROUND: We previously showed that the bacterial lipopeptide Pam3Cys-Ser-Ser, meanwhile established as a toll-like receptor (TLR) 1/2 ligand, acts as a strong adjuvant for the induction of virus specific CD8+ T cells in mice, when covalently coupled to a synthetic peptide.CASE PRESENTATION: We now designed a new water-soluble synthetic Pam3Cys-derivative, named XS15 and characterized it in vitro by a TLR2 NF-κB luciferase reporter assay. Further, the capacity of XS15 to activate immune cells and stimulate peptide-specific CD8+ T and NK cells by 6-sulfo LacNAc+ monocytes was assessed by flow cytometry as well as cytokine induction using immunoassays. The induction of a functional immune response after vaccination of a volunteer with viral peptides was assessed by ELISpot assay and flow cytometry in peripheral blood cells and infiltrating cells at the vaccination site, as well as by immunohistochemistry and imaging. XS15 induced strong ex vivo CD8+ and TH1 CD4+ responses in a human volunteer upon a single injection of XS15 mixed to uncoupled peptides in a water-in-oil emulsion (Montanide™ ISA51 VG). A granuloma formed locally at the injection site containing highly activated functional CD4+ and CD8+ effector memory T cells. The total number of vaccine peptide-specific functional T cells was experimentally assessed and estimated to be 3.0 × 105 in the granuloma and 20.5 × 106 in peripheral blood.CONCLUSION: Thus, in one volunteer we show a granuloma forming by peptides combined with an efficient adjuvant in a water-in-oil-emulsion, inducing antigen specific T cells detectable in circulation and at the vaccination site, after one single vaccination only. The ex vivo T cell responses in peripheral blood were detectable for more than one year and could be strongly boosted by a second vaccination. Hence, XS15 is a promising adjuvant candidate for peptide vaccination, in particular for tumor peptide vaccines in a personalized setting.

U2 - 10.1186/s40425-019-0796-5

DO - 10.1186/s40425-019-0796-5

M3 - SCORING: Journal article

C2 - 31730025

VL - 7

SP - 307

JO - J IMMUNOTHER CANCER

JF - J IMMUNOTHER CANCER

SN - 2051-1426

IS - 1

ER -