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Nat Genet ; 51(6): 1035-1043, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31133745

RESUMO

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.


Assuntos
Genômica , Vacinas Estreptocócicas/genética , Vacinas Estreptocócicas/imunologia , Streptococcus pyogenes/genética , Streptococcus pyogenes/imunologia , Antígenos de Bactérias/genética , Antígenos de Bactérias/imunologia , Genoma Bacteriano , Estudo de Associação Genômica Ampla , Genômica/métodos , Humanos , Filogenia , Recombinação Genética , Infecções Estreptocócicas/prevenção & controle , Streptococcus pyogenes/classificação
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