Protection against group B Neisseria meningitidis disease: effect of serogroup B polysaccharide and polymyxin B on immunogenicity of serotype protein preparations

Abstract

The inability to prepare an effective polysaccharide vaccine against group B Neisseria meningitidis was the impetus for these studies. Outer membrane protein vaccines used in our initial studies failed to induce bactericidal antibodies in humans. The particulate nature of these vaccines may have led to their clearance before effective immune stimulation. Less denaturing procedures, therefore, were developed for preparation of serotype 2 protein-containing vaccines. These procedures included isolation of naturally released outer membrane vesicles and selective removal of lipopolysaccharide from the vesicles by the nonionic detergent Brij-96. The resultant protein vaccines were evaluated with and without noncovalently complexed group B meningococcal polysaccharide or polymyxin B sulfate or both. The new vaccines were at least 10-fold more immunogenic in mice and guinea pigs than the previous vaccines when assayed for bactericidal and enzyme-linked immunosorbent assay antibodies. The protein vaccines alone protected guinea pigs from intrachamber infection, and a single 0.1-microgram injection prevented meningococcal bacteremia in mice. Addition of group B polysaccharide to the protein significantly improved the immunogenicity of the protein, and this combined vaccine showed a greater protective effect. Polymyxin B generally reduced the immunogenicity of the vaccines in both mice and guinea pigs.