Induction of meningococcal group B polysaccharide-specific IgG antibodies in mice by using an N-propionylated B polysaccharide-tetanus toxoid conjugate vaccine

J Immunol. 1986 Sep 1;137(5):1708-13.

Abstract

Conjugation of the group B meningococcal polysaccharide to tetanus toxoid failed to substantially enhance its immunogenicity in mice. Therefore, additional chemical manipulation of the basic structure of the group B meningococcal polysaccharide was attempted, on the premise that a synthetically derived artificial antigen might be capable of modulating the immune response in mice to produce elevated levels of cross-reactive group B meningococcal polysaccharide-specific antibodies. To achieve this, the antigenicity of the modified polysaccharide to group B meningococcal polysaccharide-specific antibodies had to be preserved, and this criterion could only be satisfied in modifications in which the carboxylate and N-carbonyl groups of the sialic acid residues of polysaccharide remained intact. Therefore, the most successful modifications were accomplished by N-deacetylation of the group B meningococcal polysaccharide with strong base to yield a precursor that could then be N-acetylated or N-arylated with different substituents. For example, the introduction of N-propionyl groups, followed by conjugation of the resultant N-propionylated group B meningococcal polysaccharide to tetanus toxoid, yielded an antigen that when injected in mice induced in them high levels of cross-reactive group B meningococcal polysaccharide-specific IgG antibodies. The T cell dependency of this antigen was established when it was demonstrated that the levels of these B polysaccharide-specific antibodies could be significantly boosted by using both the N-propionylated- and native N-acetylated-group B meningococcal polysaccharide-tetanus toxoid conjugates.

MeSH terms

  • Animals
  • Antibodies, Bacterial / biosynthesis*
  • Antibody Specificity
  • Antigens, Bacterial / immunology*
  • Bacterial Capsules
  • Cross Reactions
  • Immunoglobulin G / biosynthesis*
  • Immunologic Memory
  • Mice
  • Neisseria meningitidis / immunology*
  • Polysaccharides, Bacterial / immunology*
  • Structure-Activity Relationship
  • Tetanus Toxoid / immunology*

Substances

  • Antibodies, Bacterial
  • Antigens, Bacterial
  • Immunoglobulin G
  • Polysaccharides, Bacterial
  • Tetanus Toxoid
  • capsular polysaccharide, meningococcal group B