title: Primary vaccination with low dose live dengue 1 virus generates a proinflammatory, multifunctional T cell response in humans.
abstract: The four dengue virus serotypes (DENV-1-DENV-4) have a large impact on global health, causing 50-100 million cases of dengue fever annually. Herein, we describe the first kinetic T cell response to a low-dose DENV-1 vaccination study (10 PFU) in humans. Using flow cytometry, we found that proinflammatory cytokines, IFNγ, TNFα, and IL-2, were generated by DENV-1-specific CD4(+) cells 21 days post-DENV-1 exposure, and their production continued through the latest time-point, day 42 (p<0.0001 for all cytokines). No statistically significant changes were observed at any time-points for IL-10 (p = 0.19), a regulatory cytokine, indicating that the response to DENV-1 was primarily proinflammatory in nature. We also observed little T cell cross-reactivity to the other 3 DENV serotypes. The percentage of multifunctional T cells (T cells making ≥ 2 cytokines simultaneously) increased with time post-DENV-1 exposure (p<0.0001). The presence of multifunctional T cells together with neutralizing antibody data suggest that the immune response generated to the vaccine may be protective. This work provides an initial framework for defining primary T cell responses to each DENV serotype and will enhance the evaluation of a tetravalent DENV vaccine.
authors: Vaccine Testing Center and Unit of Infectious Diseases, Department of Medicine, University of Vermont College of Medicine, Burlington, Vermont, United States of America. janet.lindow@uvm.edu
authors: Janet C
authors: JC
authors: Lindow
authors: Nathan
authors: N
authors: Borochoff-Porte
authors: Anna P
authors: AP
authors: Durbin
authors: Stephen S
authors: SS
authors: Whitehead
authors: Kelly A
authors: KA
authors: Fimlaid
authors: Janice Y
authors: JY
authors: Bunn
authors: Beth D
authors: BD
authors: Kirkpatrick
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003429:Cross Reactions; D016207:Cytokines / Q000378:metabolism*; D003715:Dengue; D053059:Dengue Vaccines / Q000008:administration & dosage / Q000276:immunology*; D003716:Dengue Virus / Q000276:immunology*; D005434:Flow Cytometry; D006805:Human Experimentation; D006801:Humans; D013997:Time Factors; D014611:Vaccination / Q000379:methods*
chemical_list: D016207:Cytokines; D053059:Dengue Vaccines