Research Project
2421646
The development of effective adjuvants is essential for enhancing the potency and safety of existing vaccines and for endowing low-molecular weight synthetic antigens with sufficient immunogenicity to insure the efficacy of synthetic vaccines. Ribi ImmunoChem's longstanding interest in the development of adjuvants for cancer and infectious disease vaccines has led to the discovery of a novel synthetic glycolipid which appears to enhance the activity of the principal cell types responsible for generating immunity, resulting in both strong cellular and humoral (antibody) responses in animal models. The principal goal of this Phase I research proposal is to initiate an investigation of structure-activity relationships (SAR) within this new class of synthetic monosaccharide adjuvants in order to identify an adjuvant compound for further molecular modification and/or potential clinical development. It is anticipated that this novel glycolipid will be very amenable to systematic SAR studies. The use of common advanced intermediates in the synthetic design not only allows for the preparation of a variety of monosaccharide derivatives but also augers well for scale-up processes and the creation of synthetic vaccines comprised of adjuvant-antigen conjugates. Further, it is envisioned that the amphipathic nature of these novel monosaccharides will permit non-covalent amplification using liposome technology - providing a means for slow release and oral administration as well. PROPOSED COMMERCIAL APPLICATION: This new class of synthetic monosaccharides has potential application to 1) the improvement of existing human vaccines for infectious diseases and cancer, and 2) the development of new and/or holly synthetic human vaccines.
