Development of glycoconjugate vaccines for schistosomiasis

Schistosomiasis is a debilitating parasitic disease of humans and endemic in the tropics. Although the mortality attributed to schistosomiasis is second only to malaria, surprisingly, it remains largely neglected and research efforts towards developing a protective vaccine are minimal. In my studies, I have sought to dissect the humoral immune responses to defined schistosome glycan epitopes in humans, rhesus monkeys, and mice. Using glycopeptides terminating with schistosome specific glycan epitopes, I have helped to develop a defined schistosome glycan microarray to show that while rhesus monkeys generate predominantly high titer anti-core xylose/core fucose IgG antibodies, humans generate low titer antibodies to the same epitope. Interestingly, the peak of anti-core xylose/core fucose IgG generation in the rhesus monkeys coincides with sera from these animals having the highest schistosomula killing effect observed in vitro. Mice chronically infected with schistosomiasis generate high titer anti-LDNF IgM antibodies that are cytolytic to schistosomula in vitro. Additionally, mice immunized with BSA conjugates of LDN and Man3 generated antibodies that are cytolytic to 3h-old schistosomula in vitro. To facilitate the development of glycoconjugate candidate vaccines for schistosomiasis, I have used a commercially available chemical, p-nitrophenyl anthranilate (PNPA), as a heterobifunctional linker and helped to develop an efficient and quantitative way of conjugating glycans with a free reducing end via reductive amination to carrier proteins. Our studies support the concept of developing glycoconjugates as potential protective candidate vaccines and for generating new serodiagnostic tools for schistosomiasis. In my thesis work I show that core xylose and/or core fucose epitopes have a potential.