Dendritic Cell-Directed Vaccine against HIV
Pin Wang, University of Southern California, Los Angeles
Basic Biomedical Sciences
Innovative, Developmental, Exploratory Award (IDEA)
Infection by the human immunodeficiency virus 1 (HIV) remains an enormous challenge to global human health. Millions of people are currently infected and millions more are at risk to be infected. Based on our past experiences of dealing with various viral infections, we believe that the development of an effective vaccine is the ultimate solution to stop or slow the AIDS epidemic. A vaccine is a material preparation that stimulates our body’s immune system to generate responses against pathogens. HIV is an enveloped retrovirus that presents a challenge for vaccine strategies because it has evolved to be able to evade many of the immune mechanisms of killing. Experts have even questioned whether we will be able to develop an effective HIV vaccine. However, modest protection achieved in a recent HIV vaccine trial suggests that this is not impossible. One approach to improve these results is to quest for a better vaccine carrier capable of targeted delivery of vaccine materials to immune cells. We have devised such a carrier that is modified from HIV but carries designed antigens for stimulating strong and durable antigen-specific immune responses. One feature of this designed vaccine carrier is the directed delivery to “gatekeeper” immune cells that can subsequently instruct the immune system to mount immune responses. This project proposes to thoroughly test the ability of this novel vaccine carrier to induce virus-specific immunity against HIV or simian immunodeficiency virus (SIV) in mice. Mice will be immunized by this vaccine vehicle carrying designer antigens derived from either HIV or SIV. Immune response monitoring assays will be utilized to quantify the virus-specific immune responses in great detail. We will then use an engineered vaccinia virus carrying the HIV/SIV antigens to challenge the vaccinated mice and evaluate the levels of immune protection. Additionally, we will examine several adjuvant molecules for their ability to enhance this DC-directed vaccine modality for inducing anti-HIV/SIV immunity. If successful, the outlined studies will provide proof-of-principle in small animal models that this novel vaccine delivery is potent for eliciting HIV/SIV-specific immune responses. In the long run, these results could provide important information for the design of preclinical studies in monkeys and future clinical trials for developing an effective HIV vaccine.