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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]

PMID: 31133745

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Project description:Background21 million pregnant women worldwide (18%) are estimated to carry Group B Streptococcus (GBS), which is a risk for invasive disease in newborns, pregnant women, and stillbirths. Adults ≥ 60 years or with underlying health conditions are also vulnerable to invasive GBS disease. We undertook systematic reviews on GBS organism characteristics including: capsular polysaccharide (serotype), sequence type (multi-locus sequence types (MLST)), and virulence proteins. We synthesised data by at-risk populations, to inform vaccine development.MethodsWe conducted systematic reviews and meta-analyses to estimate proportions of GBS serotypes for at risk populations: maternal colonisation, invasive disease in pregnant women, stillbirths, infants 0-90 days age, and older adults (≥60 years). We considered regional variation and time trends (2001-2018). For these at-risk population groups, we summarised reported MLST and surface proteins.ResultsBased on 198 studies (29247isolates), 93-99% of GBS isolates were serotypes Ia, Ib, II, III, IV and V. Regional variation is likely, but data gaps are apparent, even for maternal colonisation which has most data. Serotype III dominates for infant invasive disease (60%) and GBS-associated stillbirths (41%). ST17 accounted for a high proportion of infant invasive disease (41%; 95%CI: 35-47) and was found almost exclusively in serotype III strains, less present in maternal colonisation (9%; 95%CI:6-13),(4%; 95%CI:0-11) infant colonisation, and adult invasive disease (4%, 95%CI:2-6). Percentages of strains with at least one of alp 1, alp2/3, alpha C or Rib surface protein targets were 87% of maternal colonisation, 97% infant colonisation, 93% infant disease and 99% adult invasive disease. At least one of three pilus islands proteins were reported in all strains.DiscussionA hexavalent vaccine (serotypes Ia, Ib, II, III, IV and V) might provide comprehensive cover for all at-risk populations. Surveillance of circulating, disease-causing target proteins is useful to inform vaccines not targeting capsular polysaccharide. Addressing data gaps especially by world region and some at-risk populations (notably stillbirths) is fundamental to evidence-based decision-making during vaccine design.

Dataset Information

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

Publications

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

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