The Neisseria meningitidis macrophage infectivity potentiator (MIP) protein induces cross-strain serum bactericidal activity and is a potential serogroup B vaccine candidate

A gene encoding a 29kDa protein from Neisseria meningitidis serogroup B strain MC58, with homology to the macrophage infectivity potentiator (MIP) protein of Legionella pneumophila was cloned and expressed in Escherichia coli and the purified soluble recombinant protein (rMIP) was used for immunisation studies. Analysis of the predicted amino acid sequences of MIP from 13 well-characterised meningococcal strains, isolated from carriers or patients, and differing in serogroup, serotype and subtype, showed that the protein was highly conserved (98-100%) with only three distinct sequence types found (designated I, II and III). Western blotting showed that the MIP protein was expressed at similar levels by all of these strains. Immunisation of mice with type I MC58 rMIP in detergent micelles and liposomes containing monophosphoryl lipid A (MPLA) induced high levels of surface-reactive antibodies with serum bactericidal activity (SBA) titres of 1/1024 against the homologous strain. Bactericidal antibodies were also induced with the protein in saline alone and liposomes alone (titres of 1/128), but not following adsorption to Al(OH)3. Significantly, antisera raised against type I rMIP administered in saline or liposomes killed strains of heterologous sequence types II and III, with similar SBA titres (1/128-256). Taken together, these findings suggest that rMIP can provide cross-strain protection against meningococci and should be considered as a potential antigen for inclusion in new vaccines against meningococcal infection