Distribution and genetic variability of three vaccine components in a panel of strains representative of the diversity of serogroup B meningococcus

Neisseria meningitidis GNA2132, a heparin-binding protein that induces protective immunity in humans

“…Several epidemiology studies have been conducted to asses the presence and conservation of genes coding for the antigens included in the recombinant MenB vaccine (17)(18)(19)(20). Considering that the nhba gene is present in all of the strains analyzed so far and that, despite amino acid sequence variations, it showed cross-protective activity for most of the strains tested in preclinical studies (5), we believe NHBA is an important antigen to be included in a meningococcal vaccine.…”

Bexsero

“…For example, only 50% of invasive meningococcal isolates are known to produce NadA in detectable quantities (nadA expression is phase variable) with a significant proportion of the NadA negative isolates not having the nadA gene at all. 41,42 NHBA on the other hand, appears to be present in all isolates tested so far, but sequence variability is high with both a large number of alleles and significant variability at the protein sequence level, particularly in the N-terminal domain. In results presented so far antibodies against NHBA do not seem to mediate SBA against a broad group of strains.…”

“…51 More specifically, nadA is present in almost all strains belonging to the hypervirulent clonal complexes ST-32, ST-11 and ST-8, whereas it is always absent in the ST-41/44 clonal complex. Five sequence variants have been described, 42 with three of them being highly conserved (NadA-1, NadA-2 and NadA-3). NadA-4, was described to be associated only to carrier strains.…”

“…The initial approach based on obtaining the sequence of the allele variants of the major antigens 42 that are circulating in neisserial populations, revealed the rather extensive variation present in PorA, fHbp, and NHBA major antigens. Furthermore, sequence homology (or lack of it) predicts only the ability of a given vaccine to induce SBA against strains sharing the same PorA subtype.…”

“…fHbp has three major variants, but the number of individual unique sequences is now beyond 420. fHbp in the Bexsero vaccine is a protein ID 1, Novartis variant v1.1, a sub-family B, modular group I amino acid sequence, while NHBA with 14 variants reported so far 42 is a variant 1.2. In addition to the variability at the amino acid sequence level, and hence of the cross-reactivity of the induced antibody response, the ability of a serum to kill a target meningococcal isolate also depends on the amount of specific antigen in the outer membrane of each isolate.…”