Development and pre-clinical evaluation of a synthetic oligosaccharide-protein conjugate vaccine against Neisseria meningitidis serogroup C.

Significant improvement has been made in the development of vaccines against Neisseria meningitidis infections since the introduction of polysaccharide-protein conjugate vaccines. Conventional bacterial capsular polysaccharide (PS) based conjugate vaccines require unique and expensive manufacturing facilities, complex production processes and extensive quality testing. Synthetic oligosaccharide (OS) based approach is one of the novel technologies that is being developed to simplify production of conjugate vaccines. OSs can be chemically synthesized to a desired length long enough to represent the antigenic epitopes which often present as a homogenous mixture. We prepared OSs corresponding to tetramer and octamer of N. meningitidis serogroup C (MenC) PS by organic synthesis. The MenC tetramer and octamer were further conjugated with tetanus toxoid to produce respective monovalent conjugates having the desired physico-chemical characteristics. The conjugates were evaluated in a mouse model for immunogenicity and compared with a licensed PS conjugate vaccine. Synthetic conjugates could induce anti-MenC PS IgG as well as serum bactericidal titers at levels comparable to those elicited by the licensed vaccine. The increase in length of synthetic oligomers from tetramer to octamer did not appear to increase immunogenicity. The results establish the pre-clinical proof of concept for a synthetic MenC oligosaccharide conjugate vaccine candidate.

Rapid processes for purification of capsular polysaccharides from Neisseria meningitidis serogroups A and C.

The glycoconjugate vaccines against Neisseria meningitidis are highly effective, however most of these vaccines are expensive and still out of reach in the developing world as well as the technical know-how and the set-up required for the consistent production of pure polysaccharide is limited. Our laboratory has developed rapid, efficient and scalable processes for the downstream purification of N. meningitidis serogroup A (MenA) and serogroup C (MenC) capsular polysaccharides (PS). The MenC-PS was purified with a novel 2-step procedure including de-O-acetylation and hydrophobic interaction chromatography whereas, MenA-PS was purified using a rapid method as compared to the prior art. The purified PSs were analyzed by various analytical tests including nuclear magnetic resonance, molecular weight, composition and purity analyses to meet desired specifications. Our results provide a proof of principle for the purification of MenA-PS and MenC-PS with reduced timelines.