Most healthy adults are protected from
meningococcal disease by the presence of naturally acquired anti-meningococcal
antibodies; however, the identity of the target
antigens of this protective immunity remains unclear, particularly for protection against serogroup B disease. To identify the
protein targets of natural protective immunity we developed an immunoprecipitation and proteomics approach to define the immunoproteome of the meningococcus. Sera from 10 healthy individuals showing serum bactericidal activity against both a meningococcal C strain (L91543) and the B strain MC58, together with commercially available pooled human sera, were used as probe
antisera. Immunoprecipitation was performed with each serum sample and live cells from both meningococcal strains. Immunoprecipitated
proteins were identified by MS. Analysis of the immunoproteome from each serum demonstrated both pan-reactive
antigens that were recognized by most sera as well as subject-specific
antigens. Most
antigens were found in both meningococcal strains, but a few were strain-specific. Many of the immunoprecipitated
proteins have been characterized previously as
surface antigens, including adhesins and
proteases, several of which have been recognized as
vaccine candidate
antigens, e.g.
factor H-
binding protein, NadA and
neisserial heparin-binding antigen. The data demonstrate clearly the presence of meningococcal
antibodies in healthy individuals with no history of
meningococcal infection and a wide diversity of immune responses. The identification of the immunoreactive
proteins of the meningococcus provides a basis for understanding the role of each
antigen in the natural immunity associated with carriage and may help to design vaccination strategies.