title: 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.
authors.affiliation: Marshall Centre for Infectious Disease Research and Training, School of Pathology and Laboratory Medicine, University of Western Australia, Perth, Australia.
authors.forename: Shakeel
authors.initials: S
authors.lastname: Mowlaboccus
authors.affiliation: Marshall Centre for Infectious Disease Research and Training, School of Pathology and Laboratory Medicine, University of Western Australia, Perth, Australia.
authors.forename: Timothy T
authors.initials: TT
authors.lastname: Perkins
authors.affiliation: Public Health Microbiology, Forensic and Scientific Services, Health Support Queensland Department of Health, Brisbane, Australia.
authors.forename: Helen
authors.initials: H
authors.lastname: Smith
authors.affiliation: Sir Albert Sakzewski Virus Research Centre, Queensland Paediatric Infectious Diseases Laboratory, Royal Children's Hospital, Brisbane, Australia.
authors.forename: Theo
authors.initials: T
authors.lastname: Sloots
authors.affiliation: Sir Albert Sakzewski Virus Research Centre, Queensland Paediatric Infectious Diseases Laboratory, Royal Children's Hospital, Brisbane, Australia.
authors.forename: Sarah
authors.initials: S
authors.lastname: Tozer
authors.affiliation: Marshall Centre for Infectious Disease Research and Training, School of Pathology and Laboratory Medicine, University of Western Australia, Perth, Australia.
authors.forename: Lydia-Jessica
authors.initials: LJ
authors.lastname: Prempeh
authors.affiliation: Marshall Centre for Infectious Disease Research and Training, School of Pathology and Laboratory Medicine, University of Western Australia, Perth, Australia.
authors.forename: Chin Yen
authors.initials: CY
authors.lastname: Tay
authors.affiliation: Marshall Centre for Infectious Disease Research and Training, School of Pathology and Laboratory Medicine, University of Western Australia, Perth, Australia.
authors.forename: Fanny
authors.initials: F
authors.lastname: Peters
authors.affiliation: Department of Microbiology, QEII Medical Centre, PathWest Laboratory Medicine WA, Perth, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Speers
authors.affiliation: Department of Microbiology, Princess Margaret Hospital for Children, PathWest Laboratory Medicine WA, Perth, Australia.
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Keil
authors.affiliation: Marshall Centre for Infectious Disease Research and Training, School of Pathology and Laboratory Medicine, University of Western Australia, Perth, Australia.|Telethon Kids Institute, Perth, WA, Australia.
authors.forename: Charlene M
authors.initials: CM
authors.lastname: Kahler
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D040961:Genetic Drift; D016680:Genome, Bacterial; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D016013:Likelihood Functions; D008589:Meningococcal Infections / Q000453:epidemiology / Q000517:prevention & control*; D022401:Meningococcal Vaccines / Q000276:immunology* / Q000627:therapeutic use; D008875:Middle Aged; D038541:Neisseria meningitidis, Serogroup B / Q000235:genetics*; D065288:Serogroup; D014904:Western Australia; D055815:Young Adult
chemical_list: C570015:4CMenB vaccine; D000942:Antigens, Bacterial; D022401:Meningococcal Vaccines