Grant: Vaccines of the 21st Century

CD4+ T cells are required for generation and maintenance of cytotoxic CD8+ T cells playing a critical role in control of human immunodeficiency virus type-1 (HIV-1) proliferation. However, CD4+ T cell depletion usually occurs in acquired immunodeficiency syndrome (AIDS) patients due to the viral cytopathic effect derived from binding of trimeric gp120 to CD4 of T cells. Therefore, how to stimulate efficient CD8+ cytotoxic T lymphocyte (CTL) responses in AIDS patients becomes one of the major challenges in AIDS patient therapy. Early HIV-1 proteins such as tat can broadern and enhance CD8+ CTL responses against late HIV-1 proteins such as gp120 and gag. Recently, we have developed a new vaccine by using dendritic cell-repeased exosome (EXO)-targeted active T (aTexo) cell vaccine capable of stimulating CD8+ CTL responses in absence of CD4+ T cells. In this proposal, we plan to develop a novel combined early and late HIV-1 protein-specific aTexo vaccine capable of overcoming CD4+ T cell deficiency and immune suppression and stimulating effective gp120-/gag-specific CD8+ CTL responses in AIDS patients with immune suppression and declined CD4+ T cells.