Temporal Changes in BEXSERO® Antigen Sequence Type Associated with Genetic Lineages of Neisseria meningitidis over a 15-Year Period in Western Australia

Abstract

Neisseria meningitidis is the causative agent of invasive meningococcal disease (IMD). The BEXSERO® vaccine which is used to prevent serogroup B disease is composed of four sub-capsular protein antigens supplemented with an outer membrane vesicle. Since the sub-capsular protein antigens are variably expressed and antigenically variable amongst meningococcal isolates, vaccine coverage can be estimated by the meningococcal antigen typing system (MATS) which measures the propensity of the strain to be killed by vaccinated sera. Whole genome sequencing (WGS) which identifies the alleles of the antigens that may be recognised by the antibody response could represent, in future, an alternative estimate of coverage. In this study, WGS of 278 meningococcal isolates responsible for 62% of IMD in Western Australia from 2000–2014 were analysed for association of genetic lineage (sequence type [ST], clonal complex [cc]) with BEXSERO® antigen sequence type (BAST) and MATS to predict the annual vaccine coverage. A hyper-endemic period of IMD between 2000–05 was caused by cc41/44 with the major sequence type of ST-146 which was not predicted by MATS or BAST to be covered by the vaccine. An increase in serogroup diversity was observed between 2010–14 with the emergence of cc11 serogroup W in the adolescent population and cc23 serogroup Y in the elderly. BASTs were statistically associated with clonal complex although individual antigens underwent antigenic drift from the major type. BAST and MATS predicted an annual range of 44–91% vaccine coverage. Periods of low vaccine coverage in years post-2005 were not a result of the resurgence of cc41/44:ST-146 but were characterised by increased diversity of clonal complexes expressing BASTs which were not predicted by MATS to be covered by the vaccine. The driving force behind the diversity of the clonal complex and BAST during these periods of low vaccine coverage is unknown, but could be due to immune selection and inter-strain competition with carriage of non-disease causing meningococci.

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

“…Sequence analyses were performed according to the analyses used by Mowlaboccus et al [ 13 ]. Briefly, the SRST2 pipeline [ 14 ] was used to determine the alleles at the MLST loci ( abcZ , adk , aroE , fumC , gdh , pdhC and pgm ) and the alleles for fHbp , nadA , nhba , porA and fetA .…”

“…The Bexsero ® antigen sequence type (BAST) scheme has been developed to reliably monitor the prevalence of vaccine antigens in circulating meningococcal strains [ 12 ]. Mowlaboccus et al [ 13 ] have recently reported temporal changes in the BAST profiles of meningococci circulating in WA during the 2000–2014 time period. Despite no vaccine selection pressure, these changes were driven by variations in and within the circulating genetic lineages which resulted in variable (44–91%) predicted annual vaccine coverage over this time period.…”

“…To determine whether the observations made by Mowlaboccus et al [ 13 ] also apply nationally, the current study compares the population and antigenic structures of meningococci circulating in WA to those in VIC, over a five-year period (2008–12). During this study period, the notification rate of IMD was on average 0.9 and 1.0 per 100,000 population in VIC and WA, respectively.…”

Meningococcal Deduced Vaccine Antigen Reactivity (MenDeVAR) Index: a Rapid and Accessible Tool that Exploits Genomic Data in Public Health and Clinical Microbiology Applications

“…For Bexsero ® vaccine, MATS studies (29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41) were identified through literature searches. With the exception of two studies (34,40) that used PBT for fHbp of 0.012, all other antigen RP were assessed against the PBT of 0.021 for fHbp, 0.294 for NHBA, and 0.009 for NadA (18).…”

Whole genome sequencing as a novel approach for characterising Neisseria meningitidis in Australia

“…Invasive strains of N. meningitidis express a polysaccharide capsule, which is used to classify the bacteria phenotypically into one of 12 serogroups -A, B, C, E, G, I, K, L, W, X, Y and Z 5 . IMD is predominantly caused by six serogroups (A, B, C, W, X and Y) and the distribution of these serogroups varies geographically and temporally 6,7 . The MLST scheme…”