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 Saudi Arabia . 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 unexpectedly shown lack of B cell memory. Children receiving primary immunizations with protein conjugated group A polysaccharide did not show a booster response when subsequently vaccinated with native polysaccharide. This is in contrast to similar studies using Haemophilus influenzea group B (HIB) conjugate vaccines followed by HIB polysaccharide, or Meningococcal group C conjugate vaccines followed by native group C meningococcal polysaccharide. 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 was de-O-acetylated using alkaline hydrolysis. This reaction is currently being optimized to ensure preservation of polysaccharide length. Preliminary ELISA inhibition assays suggest that antibodies raised in response to immunization with the native group A polysaccharide are not inhibited as well by de-O-acetylated polysaccharide as they are by native polysaccharide suggesting the O-acetyl groups of group A meningococcal polysaccharide are immunologically important. These studies are critical to understanding, regulation and review of ongoing IND studies involving meningococcal conjugate vaccines.
