Characterization of fHbp, nhba (gna2132), nadA, porA, and sequence type in group B meningococcal case isolates collected in England and Wales during January 2008 and potential coverage of an investigational group B meningococcal vaccine

Abstract

Invasive disease caused by meningococcal capsular groups A, C, W-135, and Y is now preventable by means of glycoconjugate vaccines that target their respective polysaccharide capsules. The capsule of group B meningococci (MenB) is poorly immunogenic and may induce autoimmunity. Vaccines based on the major immunodominant surface porin, PorA, are effective against clonal epidemics but, thus far, have a limited scope of coverage against the wider MenB population at large. In an alternative approach, the first-generation, investigational, recombinant MenB (rMenB) plus outer membrane vesicle (OMV) (rMenB-OMV) vaccine contains a number of relatively conserved surface proteins, fHBP, NHBA (previously GNA2132), and NadA, alongside PorA P1.4-containing OMVs from the New Zealand MeNZB vaccine. MenB currently accounts for approximately 90% of cases of meningococcal disease in England and Wales. To assess potential rMenB-OMV vaccine coverage of pathogenic MenB isolates within this region, all English and Welsh MenB case isolates from January 2008 (n = 87) were genetically characterized with respect to fHBP, NHBA, NadA, and PorA. Alleles for fHbp, nhba, and porA were identified in all of the isolates, of which 22% were also found to harbor nadA alleles. On the basis of genotypic data and predicted immunological cross-reactivity, the potential level of rMenB-OMV vaccine coverage in England and Wales ranges from 66% to 100%.

FIG. 1.

Clonal complex profile versus year among all English/Welsh MenB case isolates received by the HPA MRU in the Januaries of 1999, 2005, 2006, 2007, and 2008. “Other” indicates clonal complexes not present among January 2008 MenB isolates. Isolates belonging to STs that are unassigned to any CC are labeled “nt.”

FIG. 2.

porA subtype versus clonal complex for all English/Welsh MenB case isolates received by the HPA MRU in January 2008. Isolates belonging to STs that are unassigned to any CC are labeled “nt.”

FIG. 3.

Pairwise amino acid alignment of nadA-1, nadA-2, nadA-3, nadA-4, nadA-5, and the previously undescribed nadA-4/nadA-5-related variant (labeled nadA-4/5 for the purpose of the alignment). Identical pairwise amino acids are shaded in black, and similar pairwise amino acids are shaded in gray. The nadA-4/nadA-5-related variant has been un-frame shifted for the purpose of the alignment.

FIG. 4.

P-distance, neighbor-joining dendrogram of translated fHbp subvariants present among all English/Welsh MenB case isolates received by the HPA MRU in January 2008. The distribution of the subvariants among the constituent clonal complexes is represented in the adjoining bar chart. The dendrogram is drawn to scale, with the sum of the branch lengths between two subvariants representing the proportion of amino acid differences between those subvariants within the pairwise alignment. Isolates belonging to STs that are unassigned to any CC are labeled “nt.”

FIG. 5.

P-distance, neighbor-joining dendrogram of translated nhba subvariants present among all English/Welsh MenB case isolates received by the HPA MRU in January 2008. The distribution of the subvariants among the constituent clonal complexes is represented in the adjoining bar chart. The dendrogram is drawn to scale, with the sum of the branch lengths between two subvariants representing the proportion of amino acid differences between those subvariants within the pairwise alignment. Isolates belonging to STs that are unassigned to any CC are labeled “nt.”

FIG. 6.

Potential rMenB-OMV coverage specifically due to the fHBP and/or the NadA/PorA component among all English/Welsh MenB case isolates received by the HPA MRU in January 2008. (a) Potential coverage versus clonal complex; (b) overall potential coverage afforded by the three antigens. “Other” signifies isolates for which coverage is not predicted to be afforded by any of the three antigens. Isolates belonging to STs that are unassigned to any CC are labeled “nt.” The pattern key represents the charts in both panels.