Neisseria Adhesin A Variation and Revised Nomenclature Scheme

Abstract

c Neisseria adhesin A (NadA), involved in the adhesion and invasion of Neisseria meningitidis into host tissues, is one of the major components of Bexsero, a novel multicomponent vaccine licensed for protection against meningococcal serogroup B in Europe, Australia, and Canada. NadA has been identified in approximately 30% of clinical isolates and in a much lower proportion of carrier isolates. Three protein variants were originally identified in invasive meningococci and named NadA-1, NadA-2, and NadA-3, whereas most carrier isolates either lacked the gene or harbored a different variant, NadA-4. Further analysis of isolates belonging to the sequence type 213 (ST-213) clonal complex identified NadA-5, which was structurally similar to NadA-4, but more distantly related to NadA-1, -2, and -3. At the time of this writing, more than 89 distinct nadA allele sequences and 43 distinct peptides have been described. Here, we present a revised nomenclature system, taking into account the complete data set, which is compatible with previous classification schemes and is expandable. The main features of this new scheme include (i) the grouping of the previously named NadA-2 and NadA-3 variants into a single NadA-2/3 variant, (ii) the grouping of the previously assigned NadA-4 and NadA-5 variants into a single NadA-4/5 variant, (iii) the introduction of an additional variant (NadA-6), and (iv) the classification of the variants into two main groups, named groups I and II. To facilitate querying of the sequences and submission of new allele sequences, the nucleotide and amino acid sequences are available at http://pubmlst.org/neisseria/NadA/.

Susceptibility of Meningococcal Strains Responsible for Two Serogroup B Outbreaks on U.S. University Campuses to Serum Bactericidal Activity Elicited by the MenB-4C Vaccine

“…Thus, these isolates appeared to be derived from a single clone. The isolates from university A had genes encoding two of the four MenB-4C antigens (Table 2): subfamily B FHbp (ID 276, 96% identical to FHbp ID 1 in the MenB-4C vaccine) and NHba variant 2 (100% identical to NHba in MenB-4C [20,21]). The case isolates from the university B outbreak had genes encoding identical respective PorA, FHbp, NHba, and NadA variants but expressed one of two related PorB sequences (PorB3-24 or PorB3-461, with 97.6% amino acid identity).…”

“…The percent identity between the vaccine NadA antigen and strain antigen is given in parentheses. Antibodies to the vaccine antigen 2/3 are reported to cover strains with NadA-1 (20). f The MenB-4C vaccine contains NHba variant 2.…”

“…The slightly different PorB sequences indicated that the university B isolates were derived from two closely related but not identical strains. The university B isolates were matched for three of the four MenB-4C antigens: FHbp ID 1 (100% identical to FHbp in MenB-4C), NHba variant 5 (91% identical to NHba in MenB-4C), and NadA peptide 1 in variant group 1 (95% identical to NadA in MenB-4C and predicted to be covered by the NadA variant group 2/3 antigen in MenB-4C [20,21]). We selected two representative blood isolates from each outbreak for further characterization of vaccine antigen expression and susceptibility to human complement-mediated serum bactericidal activity ( Table 2).…”

Meningococcal serogroup B vaccine (4CMenB): Booster dose in previously vaccinated infants and primary vaccination in toddlers and two-year-old children

“…4CMenB contains three major recombinant proteins [12][13][14] factor H-binding protein (fHbp), Neisseria adhesin A (NadA), and Neisserial Heparin Binding Antigen (NHBA) -identified by reverse vaccinology (fHbp and NHBA as fusion proteins with other recombinant proteins), and OMV from the New Zealand outbreak strain (NZ98/254) in which the immunodominant antigen is PorA 1.4. The vaccine was supplied in prefilled syringes, each 0.5 mL dose containing 50 g (each) fHbp as a recombinant protein fused with the accessory protein Genome-derived Neisseria antigen (GNA) 2091, NadA, and NHBA fused with GNA1030, 25 g NZ 98/254 OMV and 1.5 mg aluminum hydroxide as an adsorbent.…”

Phage display revisited: Epitope mapping of a monoclonal antibody directed againstNeisseria meningitidisadhesin A using the PROFILER technology

“…Group I variants are the most represented and highly cross-protective. 3,4 NadA induces high levels of bactericidal antibodies in humans, [5][6][7] and is one of the 3 recombinant proteins that are included in a broadly protective anti-MenB vaccine, designated as Bexsero Ò . Like other trimeric autotransporter adhesins, NadA is made of a C-terminal b-barrel, which anchors the protein to the outer membrane, a central a-helical coiled-coil domain (stalk) and an N-terminal "head.…”