Atlas of group A streptococcal vaccine candidates compiled using large-scale comparative genomics
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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.
Davies , M R , McIntyre , L , Mutreja , A , Lacey , J A , Lees , J A , Towers , R J , Duchêne , S , Smeesters , P R , Frost , H R , Price , D J , Holden , M T G , David , S , Giffard , P M , Worthing , K A , Seale , A C , Berkley , J A , Harris , S R , Rivera-Hernandez , T , Berking , O , Cork , A J , Torres , R S L A , Lithgow , T , Strugnell , R A , Bergmann , R , Nitsche-Schmitz , P , Chhatwal , G S , Bentley , S D , Fraser , J D , Moreland , N J , Carapetis , J R , Steer , A C , Parkhill , J , Saul , A , Williamson , D A , Currie , B J , Tong , S Y C , Dougan , G & Walker , M J 2019 , ' Atlas of group A streptococcal vaccine candidates compiled using large-scale comparative genomics ' , Nature Genetics , vol. 51 , no. 6 , pp. 1035-1043 . https://doi.org/10.1038/s41588-019-0417-8
Copyright © The Author(s), under exclusive licence to Springer Nature America, Inc. 2019. This work has been made available online in accordance with the publisher’s policies. This is the author created, accepted version manuscript following peer review and may differ slightly from the final published version. The final published version of this work is available at https://doi.org/10.1038/s41588-019-0417-8
DescriptionThis work was supported by National Health and Medical Research Council project and program grants for: Protein Glycan Interactions in Infectious Diseases and Cellular Microbiology; the Coalition to Accelerate New Vaccines Against Streptococcus (CANVAS; an Australian and New Zealand joint initiative); and The Wellcome Trust, UK. For part of this study, M.R.D. was supported by a National Health and Medical Research Council postdoctoral training fellowship (635250) and A.M. was a GENDRIVAX fellow funded by the European Union’s Seventh Framework Programme FP7/2007–2013/ under REA grant agreement number 251522.
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