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


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.

SUBMITTER: Davies MR 

PROVIDER: S-EPMC6650292 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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

Davies Mark R MR   McIntyre Liam L   Mutreja Ankur A   Lacey Jake A JA   Lees John A JA   Towers Rebecca J RJ   Duchêne Sebastián S   Smeesters Pierre R PR   Frost Hannah R HR   Price David J DJ   Holden Matthew T G MTG   David Sophia S   Giffard Philip M PM   Worthing Kate A KA   Seale Anna C AC   Berkley James A JA   Harris Simon R SR   Rivera-Hernandez Tania T   Berking Olga O   Cork Amanda J AJ   Torres Rosângela S L A RSLA   Lithgow Trevor T   Strugnell Richard A RA   Bergmann Rene R   Nitsche-Schmitz Patric P   Chhatwal Gusharan S GS   Bentley Stephen D SD   Fraser John D JD   Moreland Nicole J NJ   Carapetis Jonathan R JR   Steer Andrew C AC   Parkhill Julian J   Saul Allan A   Williamson Deborah A DA   Currie Bart J BJ   Tong Steven Y C SYC   Dougan Gordon G   Walker Mark J MJ  

Nature genetics 20190527 6


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 clinic  ...[more]

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