Synthesis of Neisseria meningitidis serogroup W135 capsular oligosaccharides for immunogenicity comparison and vaccine development.

Neisseria meningitidis (meningococcus) is a Gram-negative human pathogen that causes meningococcal diseases, such as meningococcal meningitis and meningococcal septicemia. Based on the surface capsular oligosaccharides of the organism, 13 serogroups of N. meningitidis have been identified, among which A, B, C, Y, and W135 are the major pathogenic strains. Serogroup A is the pathogen most often implicated in the seasonal epidemic disease in the developing countries of Asia and sub-Saharan Africa. Serogroups B and C cause the majority of cases in industrialized countries. Serogroups W135 and Y are responsible for the remaining cases in developing countries. The capsular polysaccharide plays an important role in bacterial pathogenesis; its antiphagocytic properties help the bacteria to escape from antibodies and complement deposition. On the other hand, the unique structure of the capsular polysaccharide also makes a good target for vaccine design. The first polysaccharide vaccine was developed in 1974; however, owing to the poor immunogenicity of polysaccharides, these vaccines typically elicit an IgM response and fail to induce T-cell-dependent immunity. Moreover, polysaccharide vaccines are poor in immunological memory, especially for children under two-years old, who belong to the major risk group of meningococcal diseases. Consequently, polysaccharide–protein conjugate vaccines were developed to improve immunogenicity. Currently, the major source of polysaccharides for vaccine preparation is from acidic lysis of bacteria and column chromatography purification. Owing to limits of purification, the obtained polysaccharide is heterogeneous and therefore, vaccine quality is inconsistent. Hence, we were interested in developing a synthesis of capsular polysaccharides with defined lengths for a homogeneous vaccine. Recently, we developed a chemical method to prepare pure N. meningitidis serogroup C capsular polysaccharide, an a(2!9) oligosialic acid glycans of defined length. Herein, we focus on the synthesis of N. meningitidis serogroup W135 capsular oligosaccharide, which consists of a glycan repeating unit of !6)-a-d-Galp-(1!4)-a-d-Neup5Ac(9OAc)-(2! (Figure 1). To the best of our knowledge, the total synthesis of this molecule has not been reported.