HIV-1 gag specific exosome-targeted CD8+ T cell based vaccine stimulates specific CTL responses leading to long-term immunity (P4493)

Abstract

Abstract The limitations of highly active anti-retroviral therapy (HAART) have necessitated the development of alternative therapeutics for human immunodeficiency virus type-1 (HIV-1)-infected patients with dysfunctional dendritic cells (DCs) and CD4+T cell deficiency. We have recently demonstrated that Con A stimulated non-specific CD8+T cells could uptake OVA pulsed DC-derived exosome (EXO), act as CD8+Tc antigen presenting cells (Th-APCs), and capable of stimulating DC- and CD4+T cell-independent OVA-specific CTL responses leading to long-term immunity. This formed the new concept novel EXO-targeted CD8+T cell vaccine. The extreme conservation and intolerance of escape variants in HIV-1 Gag p24 make it a potential target for vaccine design. In this study, we constructed adenoviral vector AdV-gag and expression vector pEGFP-gag both expressing Gag. We generated Gag specific EXO-targeted T (Gag-Texo) cell vaccine by using C57BL/6 mouse CD8+ ConA T cells with uptake of AdV-gag transfected bone marrow DC (DCgag) released EXOgag. We then generated BL6-10gag cell lines by transfection of B16 melanoma cell line (BL6-10) with pEGFP-gag. We demonstrated that Gag-Texo vaccine is capable of stimulating efficient Gag-specific CD8+ CTL responses in vivo, leading to antitumor immunity against Gag expressing B16 melanoma (BL6-10 gag) in animal studies. Therefore, this novel HIV-1-specific EXO-targeted Gag-Texo vaccine may be useful in induction of efficient CTL responses in AIDS patients.