Synthesis of the Oligosaccharides of Burkholderia pseudomallei and B. mallei Capsular Polysaccharide and Preliminary Immunological Studies of Their Protein Conjugates

Efficient strategies were developed for the synthesis of 6-deoxy-d-manno-heptopyranose and its β-(1 → 3)-linked oligomers as fragments of the common and major capsular polysaccharide, type I O-PS, of Burkholderia pseudomallei and Burkholderia mallei. The unusual heptose was synthesized from mannose, highlighted by the facile Wittig reaction and anti-Markovnikov hydroboration of the resultant olefin. The difficult β-mannosidic linkage in the oligosaccharides was achieved in high stereoselectivity by H-bond-mediated aglycone delivery. All of the oligosaccharides were conjugated with the carrier protein CRM₁₉₇. Preliminary immunological evaluations of the resultant glycoconjugates in mice verified their efficacy to elicit high titers of immunoglobulin G Antibodies and robust T-cell-dependent immune responses. It was also found that the trisaccharide conjugates provoked the strongest immune responses, worthy of further in-depth study for vaccine development.