Identification of new meningococcal serogroup B surface antigens through a systematic analysis of neisserial genomes.
The difficulty of inducing an effective immune response against the Neisseria meningitidis serogroup B capsular polysaccharide has lead to the search for vaccines for this serogroup based on outer membrane proteins. The availability of the first meningococcal genome (MC58 strain) allowed the expansion of high-throughput methods to explore the protein profile displayed by N. meningitidis. By combining a pan-genome analysis with an extensive experimental validation to identify new potential vaccine candidates, genes coding for antigens likely to be exposed on the surface of the meningococcus were selected after a multistep comparative analysis of entire Neisseria genomes. Eleven novel putative ORF annotations were reported for serogroup B strain MC58. Furthermore, a total of 20 new predicted potential pan-neisserial vaccine candidates were produced as recombinant proteins and evaluated using immunological assays. Potential vaccine candidate coding genes were PCR-amplified from a panel of representative strains and their variability analyzed using maximum likelihood approaches for detecting positive selection. Finally, five proteins all capable of inducing a functional antibody response vs N. meningitidis strain CU385 were identified as new attractive vaccine candidates: NMB0606 a potential YajC orthologue, NMB0928 the neisserial NlpB (BamC), NMB0873 a LolB orthologue, NMB1163 a protein belonging to a curli-like assembly machinery, and NMB0938 (a neisserial specific antigen) with evidence of positive selection appreciated for NMB0928. The new set of vaccine candidates and the novel proposed functions will open a new wave of research in the search for the elusive neisserial vaccine.
Pajon
Rolando
R
Meningococcal Research Department, Division of Vaccines, Center for Genetic Engineering and Biotechnology, Ave 31, Cubanacan, Habana 10600, Cuba. rfeyt@ucalgary.ca
Yero
Daniel
D
Niebla
Olivia
O
Climent
Yanet
Y
Sardiñas
Gretel
G
García
Darién
D
Perera
Yasser
Y
Llanes
Alejandro
A
Delgado
Maité
M
Cobas
Karem
K
Caballero
Evelin
E
Taylor
Stephen
S
Brookes
Charlotte
C
Gorringe
Andrew
A
D000818:Animals; D000831:Animals, Newborn; D000942:Antigens, Bacterial / Q000235:genetics* / Q000276:immunology*; D019295:Computational Biology; D004797:Enzyme-Linked Immunosorbent Assay; D016680:Genome, Bacterial / Q000235:genetics*; D022401:Meningococcal Vaccines / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D038541:Neisseria meningitidis, Serogroup B / Q000235:genetics* / Q000276:immunology*; D016133:Polymerase Chain Reaction; D051381:Rats
D000942:Antigens, Bacterial; D022401:Meningococcal Vaccines