Effects of chain length on the immunogenicity in rabbits of group B Streptococcus type III oligosaccharide-tetanus toxoid conjugates

Abstract

One method to improve the immunogenicity of polysaccharide antigens is the covalent coupling of the native polysaccharide or a derivative oligosaccharide to a carrier protein. In general T cell-dependent properties are enhanced in conjugates of smaller saccharides but a conformational epitope of the native polysaccharide may be better expressed in conjugates of larger saccharides. We have reported previously the synthesis and immunogenicity in animals of an oligosaccharide-tetanus toxdid conjugate vaccine against type III group B Streptococcus. In this study we sought to determine the optimal size of group B Streptococcus type III oligosaccharide for use in a conjugate vaccine by evaluating the relative immunogenicity of conjugate vaccines containing oligosaccharides that were twofold smaller (7000 Mr) or larger (27000 Mr) than that reported previously (14500 Mr). All three type III oligosaccharide conjugate vaccines were immunogenic in rabbits in contrast to native uncoupled group B Streptococcus type III polysaccharide. However with respect to eliciting specific antibodies that were protective in vivo the vaccine containing the intermediate-size oligosaccharide was superior to the smaller or larger conjugate vaccine. Analysis of opsonic activity of vaccine-induced antibodies demonstrated a predominance of IgG antibodies thought to reflect T cell dependence in response to shorter chain length conjugates while the conformational epitope of the native polysaccharide was maximally expressed on longer chain length conjugates. These opposing trends may account for the optimal immunogenicity of an intermediate-size group B Streptococcus type III oligosaccharide conjugate vaccine.