title: The Neisseria meningitidis macrophage infectivity potentiator protein induces cross-strain serum bactericidal activity and is a potential serogroup B vaccine candidate.
abstract: A gene encoding a 29-kDa 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 immunization studies. Analysis of the predicted amino acid sequences of MIP from 13 well-characterized meningococcal strains, isolated from carriers or patients and differing in serogroup, serotype, and subtype, showed that the protein was highly conserved (98 to 100%), with only three distinct sequence types (designated I, II, and III) found. Western blotting showed that the MIP protein was expressed at similar levels by all of these strains. Immunization 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) titers of 1/1,024 against the homologous strain. Bactericidal antibodies were also induced with the protein in saline alone and liposomes alone (titers, 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 titers (1/128 to 1/256). Taken together, these findings suggest that rMIP can provide cross-strain protection against meningococci and should be considered a potential antigen for inclusion in new vaccines against meningococcal infection.
authors.affiliation: Neisseria Research Laboratory, Molecular Microbiology, Division of Infection, Inflammation and Immunity, Sir Henry Wellcome Research Laboratories, MP814, University of Southampton Medical School, Southampton SO16 6YD, United Kingdom.
authors.forename: Miao-Chiu
authors.initials: MC
authors.lastname: Hung
authors.forename: Omar
authors.initials: O
authors.lastname: Salim
authors.forename: Jeannette N
authors.initials: JN
authors.lastname: Williams
authors.forename: John E
authors.initials: JE
authors.lastname: Heckels
authors.forename: Myron
authors.initials: M
authors.lastname: Christodoulides
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001770:Blood Bactericidal Activity; D015153:Blotting, Western; D003429:Cross Reactions; D004797:Enzyme-Linked Immunosorbent Assay; D004926:Escherichia coli / Q000235:genetics; D008264:Macrophages; D008585:Meningitis, Meningococcal / Q000276:immunology / Q000517:prevention & control / Q000628:therapy; D022401:Meningococcal Vaccines / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D038541:Neisseria meningitidis, Serogroup B / Q000235:genetics / Q000276:immunology*; D011817:Rabbits; D011994:Recombinant Proteins / Q000276:immunology; D058248:Serum Bactericidal Antibody Assay; D014614:Vaccines, Synthetic / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D001425:Bacterial Outer Membrane Proteins; D022401:Meningococcal Vaccines; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic