title: Novel meningococcal 4CMenB vaccine antigens - prevalence and polymorphisms of the encoding genes in Neisseria gonorrhoeae.
abstract: The first cross-protective Neisseria meningitidis vaccine (focus on serogroup B), the protein-based 4 component meningococcus serogroup B (4CMenB), includes the New Zealand outer membrane vesicle and three main genome-derived neisserial antigens (GNAs). These GNAs are fHbp (fused to GNA2091), NHBA (fused to GNA1030) and NadA. In this study, the prevalence and polymorphisms of the nucleotide and amino acid sequences of the 4CMenB antigens in a temporally and geographically diverse collection of N. gonorrhoeae isolates (n = 111) were investigated. All the examined GNA genes, except the nadA gene, were present in all gonococcal isolates. However, 25 isolates contained premature stop codons in the fHbp gene and/or the nhba gene, resulting in truncated proteins. Compared with the 4CMenB antigen sequences in reference strain MC58, the gonococcal strains displayed 67.0-95.4% and 60.9-94.9% identity in nucleotide sequence and amino acid sequence, respectively, in the equivalent GNA antigens. The absence of NadA, lack of universal expression of fHbp and NHBA and the uncertainty regarding the surface exposure of fHbp as well as the function of NHBA in N. gonorrhoeae will likely limit the use of the identical 4CMenB antigens in a gonococcal vaccine. However, possible cross-immunity of 4CMenB with gonococci and expression and function of the equivalent gonococcal GNAs, as well as of more appropriate GNAs for a gonococcal vaccine, need to be further examined.
authors.affiliation: WHO Collaborating Centre for Gonorrhoea and other STIs, National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Sweden.
authors.forename: Ronza
authors.initials: R
authors.lastname: Hadad
authors.forename: Susanne
authors.initials: S
authors.lastname: Jacobsson
authors.forename: Mariagrazia
authors.initials: M
authors.lastname: Pizza
authors.forename: Rino
authors.initials: R
authors.lastname: Rappuoli
authors.forename: Hans
authors.initials: H
authors.lastname: Fredlund
authors.forename: Per
authors.initials: P
authors.lastname: Olcén
authors.forename: Magnus
authors.initials: M
authors.lastname: Unemo
mesh_terms: D000595:Amino Acid Sequence; D000942:Antigens, Bacterial / Q000235:genetics* / Q000276:immunology; D001483:Base Sequence; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D006069:Gonorrhea / Q000382:microbiology / Q000517:prevention & control; D006801:Humans; D022401:Meningococcal Vaccines / Q000235:genetics* / Q000276:immunology; D008969:Molecular Sequence Data; D009344:Neisseria gonorrhoeae / Q000235:genetics* / Q000276:immunology; D038541:Neisseria meningitidis, Serogroup B / Q000235:genetics* / Q000276:immunology; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA
chemical_list: D000942:Antigens, Bacterial; D004269:DNA, Bacterial; D022401:Meningococcal Vaccines