A modular approach towards the construction of chemically-defined glycoconjugate vaccine candidates. Vaccines for many diseases pose a severe social burden and have a serious impact on the economy of endemic countries, both in human and farm animal populations. Attenuated vaccines may trigger stronger immune responses, but have important safety issues. Also, subunit and traditional conjugate vaccines, though safe, have proved poorly immunogenic and unable to trigger a response capable of generating long-term protection. Taking advantage of cutting-edge oligosaccharide synthesis and site-specific protein modification methodologies (using the malaria virus as a model system), we propose to design and synthesize chemically-defined glycoconjugate vaccine with varying carbohydrates densities, conformations, and shapes, which would rely on an easier physicochemical characterization in comparison to current carbohydrate-based vaccines, and hopefully help to elucidate the response mechanisms set in motion by these glycoproteins.
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- Synthetically Defined Glycoprotein Vaccines: Current Status & Future Directions Adamo, D.; Nilo, A.; Castagner,B.; Boutureira, O.; Berti, F.; Bernardes, G.J.L.* Chemical Science 2013, 4, 2995-3008.
- A Coordinated Synthesis and Conjugation Strategy for the Preparation of Homogeneous Glycoconjugate Vaccine Candidates Grayson, E.J.; Bernardes, G.J.L.; Chalker, J.M.; Boutureira, O.; Koeppe, J.R.; Davis, B.G. Angew. Chem. Int. Ed. 2011, 50, 4127-4132.