Development of a Neisseria meningitidis group B serotype 2b protein vaccine and evaluation in a mouse model

Abstract

Although serotype 2 remains the predominant cause of group B Neisseria meningitidis disease in many parts of the world, most cases of this disease are now due to serotype 2b rather than 2a. For this reason, we adapted the serotype 2a vaccine method of C. E. Frasch and M. S. Peppler (Infect. Immun. 37:271-280, 1982) to the production of a serotype 2b protein vaccine. A spontaneously occurring nonencapsulated mutant of the group B serotype 2b strain 3006 was obtained by selection on group B antiserum agar. Serotype 2b outer membrane protein vaccines were prepared with less than 1% lipoplysaccharide contamination. The immunogenicity of these vaccines was evaluated in mice in the presence and absence of meningococcal group B and group C capsular polysaccharides. The group B and group C polysaccharides equally potentiated the antibody response to the serotype 2b protein. Addition of aluminum hydroxide or aluminum phosphate markedly improved the antibody response to the serotype 2b protein, but aluminum hydroxide-adjuvanted vaccines consistently elicited higher antibody levels. Aluminum hydroxide-adsorbed serotype 2a and 2b protein vaccines were evaluated for induction of cross-protective bactericidal antibodies. The 2a vaccines were 2a specific, whereas the 2b vaccines elicited antibodies strongly bactericidal for both 2a and 2b meningococcal strains and protected against bacteremia in a mouse model. It may therefore be possible to provide protection against both 2a and 2b disease by using an aluminum hydroxide-adsorbed protein vaccine containing a single serotype 2 protein component.