Immunochemistry of groups A, B, and C meningococcal polysaccharide-tetanus toxoid conjugates

Abstract

The successful coupling of the meningococcal groups A, B, and C polysaccharides to tetanus toxoid to yield water soluble conjugates is described. Reactive aldehyde groups were strategically introduced into the terminal residues of the polysaccharides by the controlled periodate oxidation of the native groups B and C polysaccharides and of the group A polysaccharide previously modified by the reduction of its terminal reducing N-acetyl-mannosamine residue. This produced essentially monovalent polysaccharide molecules, which were subsequently covalently linked to tetanus toxoid by means of reductive amination. Although the groups A and C polysaccharides proved to be poor immunogens in rabbits and mice, their tetanus toxoid conjugates produced high levels of polysaccharide-specific antibodies in both animals. By contrast, even in the form of its tetanus toxoid conjugate, the group B polysaccharide failed to elicit homologous polysaccharide-specific antibodies in either animal; a major proportion of the antibodies actually produced had a specificity for the linkage area of the conjugate. This evidence is compatible with the hypothesis of the poor immunogenicity of the group B polysaccharide being structure related. Hyperimmunization of mice with the groups A and C polysaccharide-tetanus toxoid conjugates produced antisera with good bactericidal activity against their respective homologous organisms, and indicated the potential of these conjugates as potential human vaccines.