Characterization of the cell-mediated immune response to Takeda's live-attenuated tetravalent dengue vaccine in adolescents participating in a phase 2 randomized controlled trial conducted in a dengue-endemic setting
Vianney Tricou, Raphael Gottardo, Michael A Egan, Frédéric Clement, Geert Leroux-Roels, Xavier Sáez-Llorens, Astrid Borkowski, Derek Wallace, Hansi J Dean, Vianney Tricou, Raphael Gottardo, Michael A Egan, Frédéric Clement, Geert Leroux-Roels, Xavier Sáez-Llorens, Astrid Borkowski, Derek Wallace, Hansi J Dean
Abstract
Background: As robust dengue-specific CD4+ and CD8+ T cell responses are essential for protective immunity, we assessed cell-mediated immune (CMI) responses to a DENV-2-based dengue tetravalent vaccine candidate (TAK-003) in adolescents living in Panama, a dengue-endemic country.
Methods: Peripheral blood mononuclear cells were collected from a subset of 67 participants ≥ 10 years old included in a phase 2 clinical trial of TAK-003 (Clinicaltrials.gov: NCT02302066). Following stimulation with dengue peptides, the frequency, magnitude, and cross-reactivity of the CD8+ and CD4+ T cell IFN-γ, TNF-α and IL-2 responses were assessed by flow cytometry.
Results: Intracellular cytokine staining identified NS1, NS3, and NS5 as the most common non-structural (NS) targets of the CD4+ T-cell response (IFN-γ+); NS3 and NS5 were the main NS targets of the CD8+ T cell response (IFN-γ+). Both CD4+ and CD8+ T-cell responses were multi-functional (IFN-γ + TNF-α + IL-2+) and cross-reactive against DENV-1, -3, and -4 serotypes. Similar responses were seen in all CMI assessments irrespective of participant baseline status for dengue neutralizing antibodies and T cells.
Conclusions: TAK-003 elicited cross-reactive, multi-functional CD4+ and CD8+ T-cell responses, irrespective of dengue pre-exposure.
Keywords: Cell-mediated immunity; Cross-reactive; Cytokine; Dengue vaccine; Seronegative.
Conflict of interest statement
Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: VT, AB, DW, and HD are currently employed by Takeda. MAE was employed by Takeda during the study (current affiliation: AuroVaccines). RG, FC, GLR, and XSL received funding to perform the trial, the testing and/or the data analysis.
Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.
Source: PubMed