Dose-dependent T-cell Dynamics and Cytokine Cascade Following rVSV-ZEBOV Immunization
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Dose-dependent T-cell Dynamics and Cytokine Cascade Following rVSV-ZEBOV Immunization. / Dahlke, Christine; Kasonta, Rahel; Lunemann, Sebastian; Krähling, Verena; Zinser, Madeleine E; Biedenkopf, Nadine; Fehling, Sarah K; Ly, My L; Rechtien, Anne; Stubbe, Hans C; Olearo, Flaminia; Borregaard, Saskia; Jambrecina, Alen; Stahl, Felix; Strecker, Thomas; Eickmann, Markus; Lütgehetmann, Marc; Spohn, Michael; Schmiedel, Stefan; Lohse, Ansgar W; Becker, Stephan; Addo, Marylyn M; VEBCON.
in: EBIOMEDICINE, Jahrgang 19, 05.2017, S. 107-118.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Dose-dependent T-cell Dynamics and Cytokine Cascade Following rVSV-ZEBOV Immunization
AU - Dahlke, Christine
AU - Kasonta, Rahel
AU - Lunemann, Sebastian
AU - Krähling, Verena
AU - Zinser, Madeleine E
AU - Biedenkopf, Nadine
AU - Fehling, Sarah K
AU - Ly, My L
AU - Rechtien, Anne
AU - Stubbe, Hans C
AU - Olearo, Flaminia
AU - Borregaard, Saskia
AU - Jambrecina, Alen
AU - Stahl, Felix
AU - Strecker, Thomas
AU - Eickmann, Markus
AU - Lütgehetmann, Marc
AU - Spohn, Michael
AU - Schmiedel, Stefan
AU - Lohse, Ansgar W
AU - Becker, Stephan
AU - Addo, Marylyn M
AU - VEBCON
N1 - Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.
PY - 2017/5
Y1 - 2017/5
N2 - BACKGROUND: The recent West African Ebola epidemic led to accelerated efforts to test Ebola vaccine candidates. As part of the World Health Organisation-led VSV Ebola Consortium (VEBCON), we performed a phase I clinical trial investigating rVSV-ZEBOV (a recombinant vesicular stomatitis virus-vectored Ebola vaccine), which has recently demonstrated protection from Ebola virus disease (EVD) in phase III clinical trials and is currently in advanced stages of licensing. So far, correlates of immune protection are incompletely understood and the role of cell-mediated immune responses has not been comprehensively investigated to date.METHODS: We recruited 30 healthy subjects aged 18-55 into an open-label, dose-escalation phase I trial testing three doses of rVSV-ZEBOV (3×10(5) plaque-forming units (PFU), 3×10(6) PFU, 2×10(7) PFU) (ClinicalTrials.gov; NCT02283099). Main study objectives were safety and immunogenicity, while exploratory objectives included lymphocyte dynamics, cell-mediated immunity and cytokine networks, which were assessed using flow cytometry, ELISpot and LUMINEX assay.FINDINGS: Immunization with rVSV-ZEBOV was well tolerated without serious vaccine-related adverse events. Ebola virus-specific neutralizing antibodies were induced in nearly all individuals. Additionally, vaccinees, particularly within the highest dose cohort, generated Ebola glycoprotein (GP)-specific T cells and initiated a cascade of signaling molecules following stimulation of peripheral blood mononuclear cells with Ebola GP peptides.INTERPRETATION: In addition to a benign safety and robust humoral immunogenicity profile, subjects immunized with 2×10(7) PFU elicited higher cellular immune responses and stronger interlocked cytokine networks compared to lower dose groups. To our knowledge these data represent the first detailed cell-mediated immuneprofile of a clinical trial testing rVSV-ZEBOV, which is of particular interest in light of its potential upcoming licensure as the first Ebola vaccine. VEBCON trial Hamburg, Germany (NCT02283099).
AB - BACKGROUND: The recent West African Ebola epidemic led to accelerated efforts to test Ebola vaccine candidates. As part of the World Health Organisation-led VSV Ebola Consortium (VEBCON), we performed a phase I clinical trial investigating rVSV-ZEBOV (a recombinant vesicular stomatitis virus-vectored Ebola vaccine), which has recently demonstrated protection from Ebola virus disease (EVD) in phase III clinical trials and is currently in advanced stages of licensing. So far, correlates of immune protection are incompletely understood and the role of cell-mediated immune responses has not been comprehensively investigated to date.METHODS: We recruited 30 healthy subjects aged 18-55 into an open-label, dose-escalation phase I trial testing three doses of rVSV-ZEBOV (3×10(5) plaque-forming units (PFU), 3×10(6) PFU, 2×10(7) PFU) (ClinicalTrials.gov; NCT02283099). Main study objectives were safety and immunogenicity, while exploratory objectives included lymphocyte dynamics, cell-mediated immunity and cytokine networks, which were assessed using flow cytometry, ELISpot and LUMINEX assay.FINDINGS: Immunization with rVSV-ZEBOV was well tolerated without serious vaccine-related adverse events. Ebola virus-specific neutralizing antibodies were induced in nearly all individuals. Additionally, vaccinees, particularly within the highest dose cohort, generated Ebola glycoprotein (GP)-specific T cells and initiated a cascade of signaling molecules following stimulation of peripheral blood mononuclear cells with Ebola GP peptides.INTERPRETATION: In addition to a benign safety and robust humoral immunogenicity profile, subjects immunized with 2×10(7) PFU elicited higher cellular immune responses and stronger interlocked cytokine networks compared to lower dose groups. To our knowledge these data represent the first detailed cell-mediated immuneprofile of a clinical trial testing rVSV-ZEBOV, which is of particular interest in light of its potential upcoming licensure as the first Ebola vaccine. VEBCON trial Hamburg, Germany (NCT02283099).
KW - Journal Article
U2 - 10.1016/j.ebiom.2017.03.045
DO - 10.1016/j.ebiom.2017.03.045
M3 - SCORING: Journal article
C2 - 28434944
VL - 19
SP - 107
EP - 118
JO - EBIOMEDICINE
JF - EBIOMEDICINE
SN - 2352-3964
ER -
