SYNTHESIS AND IMMUNOLOGICAL EVALUATION OF A CAPSULAR POLYSACCHARIDE VARIANT OF STREPTOCOCCUS PNEUMONIAE SEROTYPE 3

Streptococcus pneumoniae is a Gram-positive bacterium and one of the main pathogen causing invasive diseases such as meningitis, otitis media, septicemia, bacteremia and pneumonia. Pneumonococcal diseases account for more than 1 million deaths worldwide, majority of them occurring in the developing countries. >90 serotypes of Streptococcus pneumoniae have been identified based on difference in their core capsular polysaccharides (CPS) structures consisting of polymer of repeating oligosaccharides units which are the virulent factor of the bacteria. Conventional Pneumococcal Conjugated Vaccines (PCV) such as Prevnar^® (PCV-7 and PCV-13) and Synflorix^®, containing a few serotypes are proven to reduce pneumococcal related diseases but are cost intensive. Developing alternative platforms such as synthetic carbohydrate vaccine with defined structures may resolve the problems associated with current carbohydrate based vaccines.

Streptococcus pneumonia serotype 3 (SP3) is part of the carbohydrate vaccines (PPV-23 valent and PCV-13 valent). Recent reports outline that current pediatric vaccine containing SP3 does not protect against all the strains of SP3.^{1, 2} Hence a comprehensive evaluation of this serotype is urgently required. In this regard, we have focused our studies on the development of a synthetic variant of SP3 based on CPS. Current work includes the synthesis of SP3 antigen using [2+2] block synthetic strategy and its conjugation to CRM197, a carrier protein. Subsequent immunization studies in mice as well as immunogenicity evaluation using glycan array showed that the tetrasaccharide variant is more immunogenic than the trisaccharide variant of SP3.