Poster Abstract >> International Carbohydrate Symposium > by Dr. Stewart Campbell

Jun 21, 2016
View an abstract of the poster to be given at the International Carbohydrate Symposium, July 17-20, 2016 at the New Orleans Marriott, LA >> by Dr. Stewart Campbell, Head of Business Development & Product Management, Carbohydrates >> Title: Protection against experimental melioidosis with a synthetic beta-manno-heptopyranose hexasaccharide glycoconjugate

Title >> Protection against experimental melioidosis with a synthetic beta-manno-heptopyranose hexasaccharide glycoconjugate

Abstract >>

Melioidosis is an infectious disease caused by Burkholderia pseudomallei and is associated with high morbidity and mortality rates in endemic areas. It is difficult to treat with antibiotics and there is no licensed vaccine. B. pseudomallei expresses a capsular polysaccharide (CPS) consisting of a homopolymer of unbranched 1-3 linked 2-O-acetyl-6-deoxy-β-D-manno-heptopyranose.  This polysaccharide is a major virulence determinant and is thought to be present in all examples of this species, offering the opportunity to develop a univalent vaccine protective against melioidosis.

Access to CPS antigen is currently through a traditional bioprocessing route. This requires expensive containment facilities and yields a product with a naturally heterogeneous chain length containing some impurities, which considerably complicates the manufacture of pharmaceutical grade vaccine. We have taken an entirely synthetic approach to access CPS antigen of defined chain length and purity well suited for development. The synthetic hexasaccharide antigen was designed to incorporate all of the defining structural characteristics of natural CPS in addition to an amine-based linker to allow efficient conjugation to protein carriers.

Antigen was synthesized using a modular assembly approach and coupled to the non-toxic Hc domain of tetanus toxin to promote recruitment of T-cell help for antigen display. Mice immunized with the glycoconjugate developed CPS-specific IgM and IgG responses. Furthermore, immunized mice were significantly protected against death in a murine challenge model. These results justify further development toward an effective vaccine.

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