Assessment of vaccine potential of the Neisseria-specific protein NMB0938.
The availability of complete genome sequence of Neisseria meningitidis serogroup B strain MC58 and reverse vaccinology has allowed the discovery of several novel antigens. Here, we have explored the potential of N. meningitidis lipoprotein NMB0938 as a vaccine candidate, based on investigation of gene sequence conservation and the antibody response elicited after immunization in mice. This antigen was previously identified by a genome-based approach as an outer membrane lipoprotein unique to the Neisseria genus. The nmb0938 gene was present in all 37 Neisseria isolates analyzed in this study. Based on amino acid sequence identity, 16 unique sequences were identified which clustered into three variants with identities ranging from 92 to 99%, with one cluster represented by the Neisseria lactamica strains. Recombinant protein NMB0938 (rNMB0938) was expressed in Escherichia coli and purified after solubilization of the insoluble fraction. Antisera produced in mice against purified rNMB0938 reacted with a range of meningococcal strains in whole-cell ELISA and western blotting. Using flow cytometry, it was also shown that anti-rNMB0938 antibodies bound to the surface of the homologous meningococcal strain and activated complement deposition. Moreover, antibodies against rNMB0938 elicited complement-mediated killing of meningococcal strains from both sequence variants and conferred passive protection against meningococcal bacteremia in infant rats. According to our results, NMB0938 represents a promising candidate to be included in a vaccine to prevent meningococcal disease.
Sardiñas
Gretel
G
Meningococcal Research Department, Division of Vaccines, Center for Genetic Engineering and Biotechnology, Cubanacan, Habana 10600, Cuba. gretel.sardinas@cigb.edu.cu
Climent
Yanet
Y
Rodríguez
Yaindrys
Y
González
Sonia
S
García
Darién
D
Cobas
Karem
K
Caballero
Evelin
E
Pérez
Yusleydis
Y
Brookes
Charlotte
C
Taylor
Stephen
S
Gorringe
Andrew
A
Delgado
Maité
M
Pajón
Rolando
R
Yero
Daniel
D
D000595:Amino Acid Sequence; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology*; D000942:Antigens, Bacterial / Q000276:immunology*; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology; D015153:Blotting, Western; D003165:Complement System Proteins / Q000276:immunology; D019295:Computational Biology; D004269:DNA, Bacterial / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D008589:Meningococcal Infections / Q000276:immunology / Q000517:prevention & control*; D022401:Meningococcal Vaccines / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D038541:Neisseria meningitidis, Serogroup B / Q000235:genetics / Q000276:immunology; D010802:Phylogeny; D051381:Rats; D011994:Recombinant Proteins / Q000276:immunology; D016415:Sequence Alignment
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D004269:DNA, Bacterial; D022401:Meningococcal Vaccines; D011994:Recombinant Proteins; D003165:Complement System Proteins