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Nat Genet. 2019 Jun;51(6):1035-1043. doi: 10.1038/s41588-019-0417-8. Epub 2019 May 27.

Atlas of group A streptococcal vaccine candidates compiled using large-scale comparative genomics.

Author information

1
Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne and The Royal Melbourne Hospital, Melbourne, Victoria, Australia. mark.davies1@unimelb.edu.au.
2
The Wellcome Trust Sanger Institute, Hinxton, UK. mark.davies1@unimelb.edu.au.
3
School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland, Australia. mark.davies1@unimelb.edu.au.
4
Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, Queensland, Australia. mark.davies1@unimelb.edu.au.
5
Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne and The Royal Melbourne Hospital, Melbourne, Victoria, Australia.
6
The Wellcome Trust Sanger Institute, Hinxton, UK.
7
GSK Vaccines Institute for Global Health, Siena, Italy.
8
Doherty Department, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne and The Royal Melbourne Hospital, Melbourne, Victoria, Australia.
9
Department of Microbiology, New York University School of Medicine, New York, NY, USA.
10
Menzies School of Health Research, Darwin, Northern Territory, Australia.
11
Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, Victoria, Australia.
12
Molecular Bacteriology Laboratory, Université Libre de Bruxelles, Brussels, Belgium.
13
Department of Pediatrics, Queen Fabiola Childrens University Hospital, Université Libre de Bruxelles, Brussels, Belgium.
14
Murdoch Childrens Research Institute, Melbourne, Victoria, Australia.
15
Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia.
16
Victorian Infectious Diseases Reference Laboratory Epidemiology Unit, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne and The Royal Melbourne Hospital, Melbourne, Victoria, Australia.
17
School of Medicine, University of St Andrews, St Andrews, UK.
18
Wellcome Trust Research Centre, Kilifi, Kenya.
19
Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
20
School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland, Australia.
21
Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, Queensland, Australia.
22
Laboratory of Bacteriology, Epidemiology Laboratory and Disease Control Division, Laboratório Central do Estado do Paraná, Curitiba, Brazil.
23
Department of Medicine, Universidade Positivo, Curitiba, Brazil.
24
Infection and Immunity Program, Biomedicine Discovery Institute and Department of Microbiology, Monash University, Melbourne, Victoria, Australia.
25
Helmholtz Centre for Infection Research, Braunschweig, Germany.
26
Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
27
Telethon Kids Institute, University of Western Australia and Perth Children's Hospital, Perth, Western Australia, Australia.
28
Microbiological Diagnostic Unit Public Health Laboratory, Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne and The Royal Melbourne Hospital, Melbourne, Victoria, Australia.
29
Victorian Infectious Disease Service, The Royal Melbourne Hospital, Melbourne, Victoria, Australia.
30
Department of Medicine, University of Cambridge, Cambridge, UK.
31
School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland, Australia. mark.walker@uq.edu.au.
32
Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, Queensland, Australia. mark.walker@uq.edu.au.

Abstract

Group A Streptococcus (GAS; Streptococcus pyogenes) is a bacterial pathogen for which a commercial vaccine for humans is not available. Employing the advantages of high-throughput DNA sequencing technology to vaccine design, we have analyzed 2,083 globally sampled GAS genomes. The global GAS population structure reveals extensive genomic heterogeneity driven by homologous recombination and overlaid with high levels of accessory gene plasticity. We identified the existence of more than 290 clinically associated genomic phylogroups across 22 countries, highlighting challenges in designing vaccines of global utility. To determine vaccine candidate coverage, we investigated all of the previously described GAS candidate antigens for gene carriage and gene sequence heterogeneity. Only 15 of 28 vaccine antigen candidates were found to have both low naturally occurring sequence variation and high (>99%) coverage across this diverse GAS population. This technological platform for vaccine coverage determination is equally applicable to prospective GAS vaccine antigens identified in future studies.

PMID:
31133745
DOI:
10.1038/s41588-019-0417-8

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