The long-term goal of this research proposal is to design an effective and safe antigen carrier for human administration. Specifically, this proposal explores the pharmacokinetics, tissue disposition, and subsequent biologic responses of candidate antigen carriers such as liposomes, immunostimulating complex (ISCOM), alum, and water/oil emulsion (Freund's adjuvant). We will study antigen and carrier interactions for the recombinant proteins of herpes simplex virus (HSV) and human immunodeficiency virus (HIV) in the absence and presence of plasma/serum. These studies together with pharmacokinetic studies performed in mice and guinea pigs will shed light on characteristics of each antigen carrier (in vitro and in vivo). Parallel biologic studies will be done with HSV and HIV antigens to evaluate the functional activities of peptide fragments generated in vivo. Data will be compared with immunogenic peptides determined by in vitro peptide mapping techniques. In addition, we will determine whether each antigen carrier may induce a difference in quantity and quality of the naturally processed peptides by further purification and sequencing of these peptides. Antibody and cell-mediated immune responses of the immunized mice and guinea pigs will also be performed to describe immune induction mechanisms of each antigen carrier. These studies will be correlated with clinical efficacy studies performed on HSV-infected guinea pigs and mice. Systematic studies of the proposed antigens and carriers will provide further understanding of the characteristics, capabilities, and limitations of each antigen and carrier combination. The findings of these studies will serve as a foundation for the systematic design of antigen carriers that potentiate optimum protective immune responses with minimum side-effects.
