Dr. Mannino indicates that new approaches to immunoprophylaxis and immunotherapy need to be actively investigated. Several years ago. his laboratory found that a substantial immune response could be induced to synthetic peptide epitopes by conjugating the peptides with a hydrophobic anchor and formulating these conjugates into a lipid matrix. The requirements for immunogenic peptide- phospholipid complexes were shown to be: the presence of a B cell epitope, the presence of a T helper cell epitope and reconstitution of these epitopes into a lipid matrix. These peptide-phospholipid complexes consist of synthetic peptides and purified lipids and are immunogenic in the absence of carrier proteins or additional adjuvants. Ongoing studies involving peptide-phospholipid complexes have had two major long term goals: 1) To utilize these well defined immunogens to elucidate fundamental principles governing the immune response, and 2) To define the characteristics of peptide-phospholipid complexes with the ultimate goal of utilizing them clinically as prophylactic and therapeutic immunogens.
The specific aims of this application are designed to continue to pursue these long term goals and include: (1) Understanding the immunological principles resulting in the induction of an antibody response to specific HIV-derived epitopes. Using this knowledge to determine how to formulate multi-epitope peptide-phospholipid complexes that can stimulate a protective antibody response. (2) Understanding the immunological principles regulating the activation of cytotoxic T lymphocytes specific to HIV-derived epitopes. Using this knowledge to determine how to formulate multi-epitope peptide-phospholipid complexes that stimulate cytotoxic T lymphocytes that decrease the pathogenesis resulting from HIV infection. (3) Investigating the ability to utilize peptide-phospholipid complexes containing only B cell epitopes to reduce or eliminate the humoral immune response to specific eptiopes in order to remove enhancing antibodies.
