Diverse pathogens expose on their surface a dense, often highly conserved array of glycan structures that exert a protective function against the host’s immune defence and are essential for their pathogenicity. Typical examples are lipopolysaccharides (LPS) of Gram-negative bacteria, the polysaccharide coat (capsular polysaccharides, CPS) of encapsulated bacteria, and glycoproteins/glycolipids specifically expressed on the surface of viruses and parasites.<br/>All these glycoforms are capable of interacting with the immune system as epitopes inducing the production of carbohydrate-specific antibodies. They, therefore, represent attractive targets for vaccine design. In this regard, glycoconjugate vaccines, based on the covalent linking to immunogenic proteins of glycan structures uniquely exposed on the surface of pathogens, give rise to conventional B cell-mediated immunological memory, and exert a satisfying immunological activity even among persons in high-risk groups. Several conjugate versions of polysaccharide vaccines are now either commercially available or in development. Additional benefits are expected from the development of a new generation of glycoconjugate vaccines based on the use of synthetic saccharide antigens. The chemical synthesis of oligosaccharides provides homogeneous and well defined molecules with built-in chemical terminal functionalities suitable for conjugation to carrier proteins. Furthermore, only chemical synthesis allows modification of glycoepitopes to break immune tolerance and improve their immunogenicity, as well as to increase their chemical stability. Accordingly, in the past decade, a variety of oligosaccharides resembling or mimicking bacterial carbohydrates have been synthesized by us and other groups, protein conjugated and proved to elicit protective antibodies in animal models.<br/>Numerous bacterial polysaccharides are phosphoglycans, in which the phosphodiester linkages connecting the saccharide repeating units are often immunologically active components and crucial virulence determinants.<br/>In the present communication, some significant examples of the contribution of our laboratory to the synthesis and immunoevaluation of bacterial phosphoglycans will be illustrated and discussed, showing how synthetic organic chemists can play a leading role in the design and development of new and more efficacious vaccines against infectious diseases.

Sweet side of immunology: Design and synthesis of neo-glycoconjugates for vaccines formulation

ACS Spring Meeting 2021

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