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.

Distinct Binding and Immunogenic Properties of the Gonococcal Homologue of Meningococcal Factor H Binding Protein

“…However, inspection of gonococcal genome reveals a homologue of fhbp (annotated as ngo0033 in N. gonorrhoeae strain FA1090); we designated the predicted protein G onococcal h omologue of f Hb p (Ghfp), because it is approximately 90% identical to V3 fHbps. In contrast to meningococcal fHbp, Ghfp is highly conserved with three alleles described which only differ by one or two amino acids [16]. Furthermore, Ghfp is not predicted to contain a signal sequence or a lipid modification motif (LXXC) suggesting it is unlikely to be expressed on the bacterial surface [16], [17].…”

Genetic Distribution of Noncapsular Meningococcal Group B Vaccine Antigens in Neisseria lactamica

“…Such an effect may be beneficial in the case of N. gonorrhoeae. A recent study investigating the genetic distribution of the 4CMenB antigens among temporally and geographically diverse N. gonorrhoeae isolates indicated the widespread presence of nhba and fhbp alleles and the absence of nadA (25). Frameshifting among significant proportions of fhbp and nhba alleles and doubts over the surface location of fHbp, however, led the authors to speculate that the potential beneficial impact of 4CMenB against N. gonorrhoeae is likely to be limited.…”

Proteomics-driven Antigen Discovery for Development of Vaccines Against Gonorrhea

“…These three proteins are formulated as part of the Bexsero meningococcal group B vaccine approved by the European commission in 2013 and the United States in February of 2015 (12,15,16). Unfortunately, N. gonorrhoeae homologs of these proteins are not suitable vaccine targets (17). Further, in contrast to meningococcal vaccines, progress on gonococcal vaccines has been hampered primarily by the absence of a vaccine-targetable surface capsule, exceptional variability of several surface antigens, a poor understanding of protective responses, and until relatively recently, the lack of a small laboratory animal model to systematically test potential vaccine candidates (16).…”