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. ELISA inhibition assays showed 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. Immunization of mice with OAc+ and OAC- Group A PS protein conjugate vaccines and OAc+ and OAc- PS vaccines have been completed. Analysis of the immune responses with ELISA and ELISA inhibition assays Also suggests the OAc groups of meningococcal group A PS contribute to important antigenic epitopes of the PS. Bactericidal assays are planned. These studies are critical to understanding the immune response to meningococcal group A plysaccharide and contribute to the regulation and review of ongoing IND studies involving meningococcal conjugate vaccines.
