Dengue Fever (DF) and
Dengue Hemorrhagic Fever (DHF) are significant global
public health problems and understanding the overall immune response to infection will contribute to appropriate management of the
disease and its potentially severe complications. Live attenuated and
subunit vaccine candidates, which are under
clinical evaluation, induce primarily an
antibody response to the
virus and minimal cross-reactive
T cell responses. Currently, there are no available tools to assess protective
T cell responses during infection or
post vaccination. Herein, we report novel, naturally processed and presented
MHC class I restricted epitopes, a subset of which binds to and activates T cells in both an HLA-A2 and HLA-A24 restricted manner. We show that
epitope specific T cells can be activated
in vivo in transgenic mice and
in vitro in seropositive and seronegative individuals and that these T cells are functional, recognizing
peptide pulsed and
dengue virus infected cells in a pro-inflammatory and cytotoxic manner. These epitopes have potential as new informational and
diagnostic tools to characterize
T cell immunity in
Dengue virus (DV) infection, and may serve as a universal vaccine candidate complementary to current vaccines in trial.