HIV-1-specific exosome targeted CD8+ T cell Vaccine. (45.24)

Abstract

Abstract Severe immuno-suppression due to immuno-tolerance and CD4 T cells depletion is the distinguishing feature of HIV-1 infection. Although highly active antiviral therapy (HAART) is available to halt progression of AIDS, it has its own inherent defects, including incomplete protection with associated side effects, and economical concerns. In addition, most of the currently available vaccines fail to induce effective CD8 CTL against HIV-1 in absence of CD4 T cells. Previously, our laboratory showed the efficacy of novel exosome (EXO)-targeted CD4 T cell vaccine (aTexo) with uptake of ova-specific dendritic (DC)-cell-released exosomes in the absence of CD4 T cells using highly metastasizing tumor model. In the present study, we find that aTexo vaccine prepared from active CD8 T cells is capable to induce CD8 CTLs, and its effect is mediated through IL-2 secretion, acquired pMHC I complexes, and partially on CD80 and CD40L costimulators. We have constructed an adenovirus-gp120 vector, which will be used to harvest gp-120-specific exosomes following DC infection, and established various tumor cell lines by transfecting gp-120 gene. We propose to generate gp-120-specific aTexo vaccine and test its efficacy in the presence or absence of CD4 T cells. These studies may significantly impact the development of novel therapeutic vaccines against HIV-1 infection.