April 21, 2020  |  

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

Authors: Davies, Mark R and McIntyre, Liam and Mutreja, Ankur and Lacey, Jake A and Lees, John A and Towers, Rebecca J and Duchêne, Sebastián and Smeesters, Pierre R and Frost, Hannah R and Price, David J and Holden, Matthew T G and David, Sophia and Giffard, Philip M and Worthing, Kate A and Seale, Anna C and Berkley, James A and Harris, Simon R and Rivera-Hernandez, Tania and Berking, Olga and Cork, Amanda J and Torres, Rosângela S L A and Lithgow, Trevor and Strugnell, Richard A and Bergmann, Rene and Nitsche-Schmitz, Patric and Chhatwal, Gusharan S and Bentley, Stephen D and Fraser, John D and Moreland, Nicole J and Carapetis, Jonathan R and Steer, Andrew C and Parkhill, Julian and Saul, Allan and Williamson, Deborah A and Currie, Bart J and Tong, Steven Y C and Dougan, Gordon and Walker, Mark J

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.

Journal: Nature genetics
DOI: 10.1038/s41588-019-0417-8
Year: 2019

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