Dengue virus specific multiple hla binding t cell epitopes for the use of universal vaccine development

Abstract

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.