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

Shakeel Mowlaboccus,Anthony D Keil,Charlene M Kahler,Kerrie Stevens,Benjamin P Howden,David J Speers,Ottar N Bjørnstad,Timothy T Perkins,Christopher A Mullally,Peter C Richmond,Guy A M Berbers

doi:10.1371/journal.pone.0186839

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.

Highlights

Invasive meningococcal disease (IMD) is caused by the Gram-negative diplococcus Neisseria meningitidis, an obligate human bacterium which cause both epidemic and endemic disease around the world [1]
In Australia, since the implementation of the Meningococcal C (MenC) conjugate vaccine on the National Immunisation Programme in 2003, there has been a significant decline in the proportion of IMD caused by serogroup C nationally
IMD is a notifiable disease in Australia and since 1994, the National Neisseria Network has been supplying information annually on the serogroup, serotype (PorB typing), serosubtype (PorA typing) and antibiotic susceptibility of invasive meningococci isolated from the eight Australian states and territories as part of the Australian Meningococcal Surveillance Programme [18]

Summary

Introduction

Invasive meningococcal disease (IMD) is caused by the Gram-negative diplococcus Neisseria meningitidis (the meningococcus), an obligate human bacterium which cause both epidemic and endemic disease around the world [1]. IMD is rare, it remains a significant public health concern due to the high mortality and morbidity rate associated with the disease globally [3]. Meningococci expressing capsule serogroups A, B, C, W, X or Y are more frequently associated with invasive disease than acapsulate strains [4,5,6] and the distribution of serogroups fluctuates geographically [7]. Conjugate and polysaccharide vaccines providing protection against meningococcal serogroups A, C, W and Y are available. In Australia, since the implementation of the Meningococcal C (MenC) conjugate vaccine on the National Immunisation Programme in 2003, there has been a significant decline in the proportion of IMD caused by serogroup C nationally. Because serogroup B polysaccharide mimics human antigens resulting in poor immunological responses, subcapsular protein-based vaccines against this serogroup have been developed. The recombinant vaccines being used in the United States and the United Kingdom are Trumenba1 [8] and Bexsero1 [9], respectively

Methods

Results

Conclusion