Group A Meningococcal disease is a significant cause of morbidity and mortality world-wide. Epidemic disease continues to develop regularly in the meningitis belt of Africa and recent epidemics have occurred in New Zealand and Australia. In the U.S., meningococcal polysaccharide vaccine is administered to all military recruits and patients with functional or anatomic asplenia. Recent studies involving investigational Group A polysaccharide-protein conjugate vaccines have yeilded unexpected results. Children receiving primary immunizations with protein conjugated group A polysaccharide do not show a booster response when subsequently vaccinated with native polysaccharide. This is in contrast to similar studies using Haemophilus influenzea type b (HIB) conjugate vaccines, or Meningococcal group C conjugate vaccines, each followed by the respective native polysaccharide. These studies suggest that the group A polysaccharide may be antigenically altered during the conjugation process. Our initial studies are focused on assessing the immunological importance of the O-acetyl groups of the native Group A meningococcal polysaccharide. Group A polysaccharide has been de-O-acetylated using alkaline hydrolysis. This reaction is currently being optimized to ensure preservation of polysaccharide chain length. Preliminary ELISA inhibition assays suggest that antibodies raised in response to immunization with native polysaccharide are not inhibited as well by de-O-acetylated polysaccharide, compared to native polysaccharide. This suggests that the O-acetyl groups are immunologically important.
