A molecular model of artificial glycoprotein with predetermined multiple immunodeterminants for gram-positive and gram-negative encapsulated bacteria

An artificial molecule was synthesized by covalently linking the oligosaccharide haptens derived frm Streptococcus pneumoniae type 6A and Neisseria meningitidis group C capsular polysaccharides to the non-toxic mutant protein CRM197, serologically related to diphtheria toxin. Immunochemical analysis using polyclonal and monoclonal antibodies showed in the glycoprotein the presence of specific immunodeterminants of the native polysaccharides and of the carrier protein. The immunological activity of this hybrid molecule tested in two animal models gave evidence for anamnestic induction of serum antibodies specifically directed to the three distinct native molecules. They neutralized the toxicity of diphtheria toxin, recognized the polysaccharide capsule of S. pneumoniae type 6A and 6B (group 6) strain and killed the N. meningitidis group C bacteria by complement-mediated bacterial lysis. These findings support the possibility of using in humans a multivalent antigen with immunogenic activity for several epidemiologically significant Gram-positive and Gram-negative encapsulated bacterial strains.