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

Mark R. Davies; Liam McIntyre; Ankur Mutreja; Jake A. Lacey; John A. Lees; Rebecca J. Towers; Sebastián Duchêne; 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; Rosângela 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

doi:10.1038/s41588-019-0417-8

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

Mark R. Davies, Liam McIntyre, Ankur Mutreja, Jake A. Lacey, John A. Lees, Rebecca J. Towers, Sebastián Duchêne, 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. CorkRosângela 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

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	1035-1043
Number of pages	9
Journal	Nature Genetics
Volume	51
Issue number	6
DOIs	https://doi.org/10.1038/s41588-019-0417-8
Publication status	Published - 1 Jun 2019

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Davies, M. R., McIntyre, L., Mutreja, A., Lacey, J. A., Lees, J. A., Towers, R. J., Duchêne, S., Smeesters, P. R., Frost, H. R., Price, D. J., Holden, M. T. G., David, S., Giffard, P. M., Worthing, K. A., Seale, A. C., Berkley, J. A., Harris, S. R., Rivera-Hernandez, T., Berking, O., ... Walker, M. J. (2019). Atlas of group A streptococcal vaccine candidates compiled using large-scale comparative genomics. Nature Genetics, 51(6), 1035-1043. https://doi.org/10.1038/s41588-019-0417-8

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title = "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.",

author = "Davies, {Mark R.} and Liam McIntyre and Ankur Mutreja and Lacey, {Jake A.} and Lees, {John A.} and Towers, {Rebecca J.} and Sebasti{\'a}n Duch{\^e}ne and Smeesters, {Pierre R.} and Frost, {Hannah R.} and Price, {David J.} and Holden, {Matthew T.G.} and Sophia David and Giffard, {Philip M.} and Worthing, {Kate A.} and Seale, {Anna C.} and Berkley, {James A.} and Harris, {Simon R.} and Tania Rivera-Hernandez and Olga Berking and Cork, {Amanda J.} and Torres, {Ros{\^a}ngela S.L.A.} and Trevor Lithgow and Strugnell, {Richard A.} and Rene Bergmann and Patric Nitsche-Schmitz 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 Julian Parkhill and Allan Saul and Williamson, {Deborah A.} and Currie, {Bart J.} and Tong, {Steven Y.C.} and Gordon Dougan and Walker, {Mark J.}",

year = "2019",

month = jun,

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doi = "10.1038/s41588-019-0417-8",

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Davies, MR, McIntyre, L, Mutreja, A, Lacey, JA, Lees, JA, Towers, RJ, Duchêne, S, Smeesters, PR, Frost, HR, Price, DJ, Holden, MTG, David, S, Giffard, PM, Worthing, KA, Seale, AC, Berkley, JA, Harris, SR, Rivera-Hernandez, T, Berking, O, Cork, AJ, Torres, RSLA, Lithgow, T, Strugnell, RA, Bergmann, R, Nitsche-Schmitz, P, Chhatwal, GS, Bentley, SD, Fraser, JD, Moreland, NJ, Carapetis, JR, Steer, AC, Parkhill, J, Saul, A, Williamson, DA, Currie, BJ , Tong, SYC, Dougan, G & Walker, MJ 2019, 'Atlas of group A streptococcal vaccine candidates compiled using large-scale comparative genomics', Nature Genetics, vol. 51, no. 6, pp. 1035-1043. https://doi.org/10.1038/s41588-019-0417-8

TY - JOUR

T1 - Atlas of group A streptococcal vaccine candidates compiled using large-scale comparative genomics

AU - Davies, Mark R.

AU - McIntyre, Liam

AU - Mutreja, Ankur

AU - Lacey, Jake A.

AU - Lees, John A.

AU - Towers, Rebecca J.

AU - Duchêne, Sebastián

AU - Smeesters, Pierre R.

AU - Frost, Hannah R.

AU - Price, David J.

AU - Holden, Matthew T.G.

AU - David, Sophia

AU - Giffard, Philip M.

AU - Worthing, Kate A.

AU - Seale, Anna C.

AU - Berkley, James A.

AU - Harris, Simon R.

AU - Rivera-Hernandez, Tania

AU - Berking, Olga

AU - Cork, Amanda J.

AU - Torres, Rosângela S.L.A.

AU - Lithgow, Trevor

AU - Strugnell, Richard A.

AU - Bergmann, Rene

AU - Nitsche-Schmitz, Patric

AU - Chhatwal, Gusharan S.

AU - Bentley, Stephen D.

AU - Fraser, John D.

AU - Moreland, Nicole J.

AU - Carapetis, Jonathan R.

AU - Steer, Andrew C.

AU - Parkhill, Julian

AU - Saul, Allan

AU - Williamson, Deborah A.

AU - Currie, Bart J.

AU - Tong, Steven Y.C.

AU - Dougan, Gordon

AU - Walker, Mark J.

PY - 2019/6/1

Y1 - 2019/6/1

N2 - 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.

AB - 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.

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DO - 10.1038/s41588-019-0417-8

M3 - Article

C2 - 31133745

AN - SCOPUS:85066634559

VL - 51

SP - 1035

EP - 1043

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 6

ER -

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

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