Meningococcal B vaccine antigen FHbp variants among disease-causing Neisseria meningitidis B isolates, Italy, 2014–2017

Abstract

Background Typing of Neisseria meningitidis isolates is crucial for the surveillance of invasive meningococcal disease (IMD). We performed a molecular epidemiology study of N. meningitidis serogroup B (MenB) causing IMD in Italy between 2014 and 2017 to describe circulating strains belonging to this serogroup, with particular regards to the two factor H-binding protein (FHbp) subfamilies present in the bivalent MenB vaccine. Materials and methods A total of 109 culture positive and 46 culture negative MenB samples were collected within the National Surveillance System (NSS) of IMD in Italy and molecularly analyzed by conventional methods. Results Overall, 71 MenB samples showed the FHbp subfamily A and 83 the subfamily B. The subfamily variants were differently distributed by age. The most frequent variants, A05 and B231, were associated with cc213 and cc162, respectively. All MenB with the FHbp A05 variant displayed the PorA P1.22,14 and 85.7% of them the FetA F5-5. The majority of MenB with the FHbp B231 variant showed the PorA P1.22,14 (65.4%) and 84.6%, the FetA F3-6. Conclusion MenB circulating in Italy were characterized by a remarkable association between clonal complex and FHbp variants, although a high degree of genetic diversity observed over time. A dynamic trend in clonal complexes distribution within MenB was detected. Our results stress the importance of continued meningococcal molecular surveillance to evaluate the potential vaccine coverage of the available MenB vaccines.

FHbp variants among meningococci of serogroup B in Italy: Evolution and selective pressure, 2014–2017

“…As reported in our previous study [ 13 ], based on a panel of MenB strains causing IMD in Italy from 2014 to 2017, the A05 variant resulted as predominant (n = 14; 19.7%), followed by A06 (n = 10; 14.1%) and A22 (n = 10; 14.1%); the B231 variant accounted for 32.5%, B03 for 13.2% and B24 for 10.8% [ 13 ]. In particular, the A05 and B231 were the most frequent variants associated with the clonal complexes cc213 and cc162, respectively [ 13 ]. All MenB with the FHbp A05 variant displayed the PorA P1.22, 14 and 85.7% of them the FetA F5-5.…”

“…The FHbp nucleotide and protein sequence alignments were performed with ClustalW [ 14 ] on 155 MenB collected from 2014 to 2017, representative of the total IMD reported within the National Surveillance System (174 MenB samples sent to ISS, of which 109 were culture positive, 46 culture negative and 19 unsuitable for molecular analysis), and previously molecular characterized within the frame of a project, the results of which were already described [ 13 ]. For the 109 culture positive MenB samples the genomes were submitted into PubMLST.org database ( http://pubmlst.org/neisseria/ ), S1 Table , and the multilocus sequence typing (MLST), PorA, FetA and FHbp typing were identified using whole genome sequencing (WGS).…”

“…All MenB with the FHbp A05 variant displayed the PorA P1.22, 14 and 85.7% of them the FetA F5-5. The A05 variant was the only identified among meningococci belonging to cc213 [ 13 ]. The majority of MenB with the FHbp B231 variant showed the PorA P1.22, 14 (65.4%) and 84.6%, the FetA F3-6 [ 13 ].…”

“…The A05 variant was the only identified among meningococci belonging to cc213 [ 13 ]. The majority of MenB with the FHbp B231 variant showed the PorA P1.22, 14 (65.4%) and 84.6%, the FetA F3-6 [ 13 ].…”

Self-assembling protein nanoparticles and virus like particles correctly display β-barrel from meningococcal factor H-binding protein through genetic fusion

“…fHbp sequences can be classified in three main variants which are generally non-cross-protective. As a highly protective antigen, fHbp is a key component of two different vaccines against MenB, namely 4C [48] MenB (Bexsero) and MenB-fHbp (Trumenba) [49][50][51]. The fHbp 3D structure is well characterized [47,52].…”