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PLoS Negl Trop Dis. 2012;6(7):e1742. doi: 10.1371/journal.pntd.0001742. Epub 2012 Jul 17.

Primary vaccination with low dose live dengue 1 virus generates a proinflammatory, multifunctional T cell response in humans.

Author information

1
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

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.

PMID:
22816004
PMCID:
PMC3398956
DOI:
10.1371/journal.pntd.0001742
[Indexed for MEDLINE]
Free PMC Article

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