The long-term goal of this project is to design an effective and safe antigen carrier for human administration. Target-selective delivery of antigen and immune enhancers using carriers has been shown to provide optimum HIV and HSV immune stimulation and to increase the margins of safety in small animal models. Recently, the highly pathogenic HIV-2 strain 287 was shown to produce rapid onset of disease in macaques similar to AIDS in humans. This macaque model is being used to determine whether the enhanced immune responses provided by antigen presenting carriers will produce clinically measurable outcomes in both virus-infected and uninfected animals. Both of these goals will be accomplished by evaluating the effects of immunizing young macaques that are either healthy or infected with HIV-2287. This virulent strain produces viremia, as well as rapid onset and progression of the disease. In both uninfected and infected infants we are working to determine whether immunization with HIV antigen presented in antigen carriers provides potent antibody and cell-mediated immune responses, to ascertain whether these enhanced or additional immune responses due to immunization translate into clinically measurable outcomes, and to characterize the key parameters that lead to positive clinical outcomes. These macaque studies will test the hypothesis that optimal presentation of antigen in the lipid carrier can provide enhanced humoral and cellular immune responses and determine whether these immune responses can prevent HIV infection and/or reduce its clinical severity. With these studies we hope to elucidate the key factors for an effective and safe antigen delivery system, thereby permitting further improvement in the potency of HIV proteins in eliciting optimal immune responses essential for prevention and treatment of AIDS.
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