Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne and The Royal Melbourne Hospital, Melbourne, Victoria, Australia.
The Wellcome Trust Sanger Institute, Hinxton, UK.
Nat Genet. 2019 Jun;51(6):1035-1043. doi: 10.1038/s41588-019-0417-8. Epub 2019 May 27.
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.
A 组链球菌（GAS; 化脓性链球菌）是一种细菌病原体，目前尚无针对人类的商业疫苗。我们利用高通量 DNA 测序技术在疫苗设计方面的优势，分析了全球采集的 2083 个 GAS 基因组。全球 GAS 种群结构揭示了由同源重组驱动的广泛基因组异质性，并叠加了高水平的辅助基因可塑性。我们在 22 个国家发现了 290 多个与临床相关的基因组进化枝，这突出了设计具有全球通用性疫苗的挑战。为了确定疫苗候选物的覆盖范围，我们研究了所有先前描述的 GAS 候选抗原的基因携带和基因序列异质性。在这个多样化的 GAS 群体中，只有 28 种疫苗抗原候选物中的 15 种具有较低的自然发生序列变异和较高（>99%）的覆盖率。这种用于确定疫苗覆盖范围的技术平台同样适用于未来研究中确定的有前景的 GAS 疫苗抗原。
