Grant: Operating Grant - PA: CHVI Vaccine Discovery and Social Research

Acquired immunodeficiency syndrome (AIDS) in human immunodeficiency virus type-1 (HIV-1)-infected patients causes millions of individuals died each year. Highly active antiviral therapy (HAART) is currently the only means to halt progression of AIDS. Although HAART suppressis viral replication and improves prognosis, it is unable to eliminate the proviral latent reservoirs by any vaccine strategies which are dependent on the functional dendritic cells (DC) and CD4+ T cells. However, AIDS patients often have dendritic cell dysfunction and CD4+ T cell dificiency. In this study, we propose to develop a combined late and early HIV-1 protein (Gp120/gag and Tat)-specific exosome (EXO)-targeted T cell-based (Gp120/gag/tat-Texo) vaccine. We will assess the therapeutic efficiency of Gp120/gag/tat-Texo vaccine against Gp120 or Gag-expressing tumor cells in wild-type C57BL/6 abd BALB/c mice and transgenic HLA-A2-expressing A2Kb mice closely mimicking the human situation. This novel Gp120/gag/tat-Texo vaccine capable of stimulating broadened efficient CTL responses and memory may thus be useful in immunotherpay of AIDS patients with DC dysfunction and declined CD4+ T cells, especially those on HAART for cleaning their proviral latent reservoirs.