Journal article

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

Mark R Davies, Liam McIntyre, Ankur Mutreja, Jake A Lacey, John A Lees, Rebecca J Towers, Sebastian Duchene, Pierre R Smeesters, Hannah R Frost, David J Price, Matthew TG Holden, Sophia David, Philip M Giffard, Kate A Worthing, Anna C Seale, James A Berkley, Simon R Harris, Tania Rivera-Hernandez, Olga Berking, Amanda J Cork Show all

NATURE GENETICS | NATURE PUBLISHING GROUP | Published : 2019

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..

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Grants

Awarded by National Health and Medical Research Council postdoctoral training fellowship


Awarded by European Union's Seventh Framework Programme FP7/2007-2013/under REA grant


Funding Acknowledgements

This 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. We acknowledge assistance from the sequencing and pathogen informatics core teams at The Wellcome Trust Sanger Institute. We acknowledge and thank the database curators of the S. pyogenes MLST and emm databases (especially D. Bessen). We dedicate this work to the memory of our friend and colleague Gusharan Singh Chhatwal.