Automated Oligosaccharide Synthesis to Create Vaccines for Malaria and Other Parasites

摘要

Malaria and leishmaniasis are two of the most devastating parasitic infections. Although much progress has been made towards the understanding and treatment of these diseases, aneffective vaccine remains elusive. To this end, our attention focused on the synthesis of malaria and leishmaniasis glycoconjugates for use as vaccine candidates. The synthesis of the malarial vaccine involved developing an "anti-disease"vaccine. Synthesis of a key portion of the malarial toxin's mannan cap was accelerated using automated solid-phase oligosaccharide synthesis methodology and, following conjugation to the protein carrier, the toxin was tested as a vaccine candidate. A series of second generation anti-disease vaccine candidates were subsequently synthesized. The key tetrasaccharide cap of the lipophosphoglycans found on the surface of leishmaniasis parasites was also synthesized, using both solution and automated solid-phase methodology, and conjugated to a protein carrier. Initial vaccination studies for both glycoproteins were encouraging.