Highly conserved Neisseria meningitidis surface protein confers protection against experimental infection.
A new surface protein, named NspA, which is distinct from the previously described Neisseria meningitidis outer membrane proteins was identified. An NspA-specific mAb, named Me-1, reacted with 99% of the meningococcal strains tested indicating that the epitope recognized by this particular mAb is widely distributed and highly conserved. Western immunoblotting experiments indicated that mAb Me-1 is directed against a protein band with an approximate molecular mass of 22,000, but also recognized a minor protein band with an approximate molecular mass of 18,000. This mAb exhibited bactericidal activity against four meningococcal strains, two isolates of serogroup B, and one isolate from each serogroup A and C, and passively protected mice against an experimental infection. To further characterize the NspA protein and to evaluate the protective potential of recombinant NspA protein, the nspA gene was identified and cloned into a low copy expression vector. Nucleotide sequencing of the meningococcal insert revealed an ORF of 525 nucleotides coding for a polypeptide of 174 amino acid residues, with a predicted molecular weight of 18,404 and a isoelectric point of 9.93. Three injections of either 10 or 20 microg of the affinity-purified recombinant NspA protein efficiently protected 80% of the mice against a meningococcal deadly challenge comparatively to the 20% observed in the control groups. The fact that the NspA protein can elicit the production of bactericidal and protective antibodies emphasize its potential as a vaccine candidate.
Martin
D
D
Unité de Recherche en Vaccinologie, Centre de Recherche en Infectiologie, Centre Hospitalier Universitaire de Québec, Ste-Foy, Canada.
Cadieux
N
N
Hamel
J
J
Brodeur
B R
BR
D000595:Amino Acid Sequence; D000818:Animals; D000907:Antibodies, Bacterial / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000942:Antigens, Bacterial / Q000627:therapeutic use*; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D001428:Bacterial Vaccines / Q000627:therapeutic use*; D001483:Base Sequence; D003001:Cloning, Molecular; D017124:Conserved Sequence; D005798:Genes, Bacterial; D007116:Immunization, Passive; D008589:Meningococcal Infections / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009345:Neisseria meningitidis / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity; D011994:Recombinant Proteins / Q000627:therapeutic use; D017422:Sequence Analysis, DNA; D014611:Vaccination
D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; C105506:NspA protein, Neisseria; D011994:Recombinant Proteins