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2 results on '"Sarah Tozer"'

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

Author

Shakeel Mowlaboccus, Timothy T Perkins, Helen Smith, Theo Sloots, Sarah Tozer, Lydia-Jessica Prempeh, Chin Yen Tay, Fanny Peters, David Speers, Anthony D Keil, and Charlene M Kahler

Subjects
Medicine, Science
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.

Published
2016
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2. Temporal Changes in BEXSERO® Antigen Sequence Type Associated with Genetic Lineages of Neisseria meningitidis over a 15-Year Period in Western Australia

Author

Helen Smith, Charlene M. Kahler, Sarah Tozer, Chin Yen Tay, Shakeel Mowlaboccus, Anthony D. Keil, Lydia-Jessica Prempeh, Theo P. Sloots, Tim Perkins, David J. Speers, and Fanny Peters

Subjects
0301 basic medicine, Physiology, lcsh:Medicine, Neisseria meningitidis, Serogroup B, Pathology and Laboratory Medicine, medicine.disease_cause, Biochemistry, Geographical Locations, 0302 clinical medicine, Antigen Encapsulation, Immune Physiology, Medicine and Health Sciences, Public and Occupational Health, 030212 general & internal medicine, Drug Delivery System Preparation, Child, lcsh:Science, Likelihood Functions, Vaccines, Immune System Proteins, Multidisciplinary, Pharmaceutics, Neisseria meningitidis, Genomics, Middle Aged, Vaccination and Immunization, Antigenic Variation, Bacterial Pathogens, 3. Good health, Medical Microbiology, Child, Preschool, Pathogens, Neisseria, Research Article, Adult, Adolescent, Immunology, Oceania, Meningococcal Vaccines, Meningococcal vaccine, Biology, Serogroup, Meningococcal disease, Microbiology, Antigenic drift, Young Adult, 03 medical and health sciences, Antigen, Genetics, medicine, Antigenic variation, Humans, Typing, Antigens, Allele, Microbial Pathogens, Alleles, Aged, Antigens, Bacterial, Bacteria, Pharmaceutical Processing Technology, Genetic Drift, lcsh:R, Infant, Newborn, Australia, Organisms, Infant, Biology and Life Sciences, Proteins, Computational Biology, Western Australia, Genome Analysis, Genomic Libraries, medicine.disease, Virology, Meningococcal Infections, 030104 developmental biology, Genetic Loci, Age Groups, People and Places, Population Groupings, lcsh:Q, Preventive Medicine, Genome, Bacterial, Neisseria Meningitidis
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.

Published
2016

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