来自澳大利亚昆士兰大学的Mark J. Walker研究组领衔完成了A族链球菌的候选疫苗图谱。该研究于2019年6月发表于国际知名学术期刊《Nature Genetics》上。

高通量DNA测序技术可用于疫苗的设计，为此研究人员分析了全球采样的2083株GAS基因组。全球GAS种群结构显示，GAS广泛存在由同源重组导致的基因组异质性，并被大量具有可塑性的附属基因所覆盖。研究人员发现在22个国家中共有超过290个临床相关的基因组谱系，因此设计全球通用的抗体具有挑战性。为确定候选疫苗的覆盖率，研究人员研究了以前报道的所有GAS候选抗原的基因的基因携带率和基因序列异质性。28个候选疫苗抗原中，只有15个存在较低的自然序列变异并在GAS种群中广泛存在（大于99%）。这个技术平台不仅可用于检测疫苗覆盖率，也用于对未来研究中GAS疫苗抗原鉴定的测试。

据介绍，A族链球菌（GAS）又称为化脓性链球菌，是一种细菌微生物，目前还没有可供人用的商业化抗体。

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

Author: Mark R. Davies, Liam McIntyre, Ankur Mutreja, Jake A. Lacey, John A. Lees, Rebecca J. Towers, Sebastin Duchne, Pierre R. Smeesters, Hannah R. Frost, David J. Price, Matthew T. G. 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, Rosngela S. L. A. Torres, Trevor Lithgow, Richard A. Strugnell, Rene Bergmann, Patric Nitsche-Schmitz, Gusharan S. Chhatwal, Stephen D. Bentley, John D. Fraser, Nicole J. Moreland, Jonathan R. Carapetis, Andrew C. Steer, Julian Parkhill, Allan Saul, Deborah A. Williamson, Bart J. Currie, Steven Y. C. Tong, Gordon Dougan, Mark J. Walker

Issue&Volume:Volume 51 Issue 6, June 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 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.

DOI: 10.1038/s41588-019-0417-8

Source:https://www.nature.com/articles/s41588-019-0417-8