Differences in the population structure of Neisseria meningitidis in two Australian states: Victoria and Western Australia

Abstract

Neisseria meningitidis is the causative agent of invasive meningococcal disease (IMD). A recombinant vaccine called Bexsero® incorporates four subcapsular antigens (fHbp, NHBA, NadA and PorA) which are used to assign a Bexsero® antigen sequence type (BAST) to each meningococcal strain. The vaccine elicits an immune response against combinations of variants of these antigens which have been grouped into specific BAST profiles that have been shown to have different distributions within geographical locations thus potentially affecting the efficacy of the vaccine. In this study, invasive meningococcal disease isolates from the western seaboard of Australia (Western Australia; WA) were compared to those from the south-eastern seaboard (Victoria; VIC) from 2008 to 2012. Whole-genome sequencing (WGS) of 131 meningococci from VIC and 70 meningococci from WA were analysed for MLST, FetA and BAST profiling. Serogroup B predominated in both jurisdictions and a total of 10 MLST clonal complexes (cc) were shared by both states. Isolates belonging to cc22, cc103 and cc1157 were unique to VIC whilst isolates from cc60 and cc212 were unique to WA. Clonal complex 41/44 represented one-third of the meningococcal population in each state but the predominant ST was locally different: ST-6058 in VIC and ST-146 in WA. Of the 108 BAST profiles identified in this collection, only 9 BASTs were simultaneously observed in both states. A significantly larger proportion of isolates in VIC harboured alleles for the NHBA-2 peptide and fHbp-1, antigenic variants predicted to be covered by the Bexsero® vaccine. The estimate for vaccine coverage in WA (47.1% [95% CI: 41.1–53.1%]) was significantly lower than that in VIC (66.4% [95% CI: 62.3–70.5%]). In conclusion, the antigenic structure of meningococci causing invasive disease in two geographically distinct states of Australia differed significantly during the study period which may affect vaccine effectiveness and highlights the need for representative surveillance when predicting potential impact of meningococcal B vaccines.

Invasive meningococcal disease epidemiology and characterization of Neisseria meningitidis serogroups, sequence types, and clones; implication for use of meningococcal vaccines

“…24 Meningococcal Antigen Typing System (MATS) has been reported to produce similar predicted vaccine coverage obtained using BAST profiling of serogroup B strains. 25 It has been suggested that induction of immunogenicity may be inferred by one of the four vaccine targets that may be sufficient to protect against invasive disease. 24 Our preliminary analysis based on limited number of N. meningitides serogroup B isolates (Israel, 2017) suggests an estimated strain coverage for 4CMenB ranging from 20% to 46.7%.…”

“…According to several BAST studies performed in various countries, the predicted strain coverage of 4CMenB vaccine according to the BAST antigens, varies between years and between countries. 24,25 A large study including 2016 confirmed IMD isolates from Great Britain and Ireland revealed variation of immunogenicity to at least one of 4 vaccine targets from 30.8% in 2010 to 22.8% in 2014. 24 A study from Australia showed a difference between 2 geographic regions, Victoria (VIC) and Western Australia (WA) in the years 2008-2012.…”

“…The fraction of either of the exact antigen variants incorporated in 4CMenB vaccine in the Serogroup B isolates was 36% in VIC, 20% in WA and 30.6% (52/170 isolates) from both regions combined. 25 The most recent UK study reporting 3073 IMD confirmed isolates during 2010-2016 showed that 36% of 1820 serogroup B isolates had exact matches to ≥ 1 4CMenB vaccine antigen variants. 26 The serogroup B isolates strain coverage range estimate for 4CMenB derived from our data is in line with the range in the above studies.…”

“…Embedded tools within PubMLST were used to analyze the presence of 4CMenB (Bexsero®) vaccine antigens (fHbp, NadA, NHBA and PorA) and Bexsero Antigen Sequence Types (BAST). 24,25 All Sequence analysis was performed with Bionumerics 7.6 (Applied Maths, Belgium)…”

Methods to evaluate serogroup B meningococcal vaccines: From predictions to real-world evidence

“…71 In certain regions in Australia, annual coverages of 44-91% were predicted by BAST and MATS, from 20 0 0 to 2014. 70,72 In addition, the European meningococcal strain collection genome library (EMSC-GL) for the epidemiological year 2011-2012 was characterized with the BAST scheme. The EMSC-GL comprised 799 meningococcal strains causing IMD, submitted by 16 European countries, of which 65.7% were MenB.…”