Outer membrane proteins of Neisseria meningitidis: structure and importance in meningococcal disease

Abstract

Meningococcal meningitis is a serious disease with a high incidence in children. Since meningococcal surface structures play a role in invasion of the host and initiation of disease, host defense mechanisms are directed against these meningococcal structures. All virulent meningococci are encapsulated, but other factors are also involved. Only certain serotypes of group B and group C meningococci are strongly associated with disease. Our studies have been directed toward a better understanding of the structure of the meningococcal cell surface. There are five classes of major outer membrane proteins exposed on the cell surface, designated class 1 through 5, based in part upon the protein's molecular weight. Using monoclonal antibodies we have shown that antibodies to the class 1, 2 and 5 proteins of serotype 2 are bactericidal and therefore probably protective. Convalescent sera of meningococcal disease patients have elevated antibody levels to each of these classes of proteins. Outer membrane protein vaccines have been prepared, and clinically evaluated in adults and children as young as 6 mo of age. The vaccines induce serotype specific bactericidal antibodies in all age groups, but they induced lower levels in young children. We are now working to improve the immune response of children through the use of aluminium adjuvants.