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 & 18 others 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

    Research output: Contribution to journalArticleResearchpeer-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 languageEnglish
    Pages (from-to)1035-1043
    Number of pages9
    JournalNature Genetics
    Volume51
    Issue number6
    DOIs
    Publication statusPublished - 1 Jun 2019

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    Streptococcal Vaccines
    Atlases
    Genomics
    Vaccines
    Antigens
    Genes
    High-Throughput Nucleotide Sequencing
    Streptococcus pyogenes
    Homologous Recombination
    Streptococcus
    Population
    Genome
    Technology

    Cite this

    Davies, M. R., McIntyre, L., Mutreja, A., Lacey, J. A., Lees, J. A., Towers, R. J., ... 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
    Davies, Mark R. ; McIntyre, Liam ; Mutreja, Ankur ; Lacey, Jake A. ; Lees, John A. ; Towers, Rebecca J. ; Duchêne, Sebastián ; Smeesters, Pierre R. ; Frost, Hannah R. ; Price, David J. ; Holden, Matthew T.G. ; David, Sophia ; Giffard, Philip M. ; Worthing, Kate A. ; Seale, Anna C. ; Berkley, James A. ; Harris, Simon R. ; Rivera-Hernandez, Tania ; Berking, Olga ; Cork, Amanda J. ; Torres, Rosângela S.L.A. ; Lithgow, Trevor ; Strugnell, Richard A. ; Bergmann, Rene ; Nitsche-Schmitz, Patric ; Chhatwal, Gusharan S. ; Bentley, Stephen D. ; Fraser, John D. ; Moreland, Nicole J. ; Carapetis, Jonathan R. ; Steer, Andrew C. ; Parkhill, Julian ; Saul, Allan ; Williamson, Deborah A. ; Currie, Bart J. ; Tong, Steven Y.C. ; Dougan, Gordon ; Walker, Mark J. / Atlas of group A streptococcal vaccine candidates compiled using large-scale comparative genomics. In: Nature Genetics. 2019 ; Vol. 51, No. 6. pp. 1035-1043.
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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.",
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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

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

    In: Nature Genetics, Vol. 51, No. 6, 01.06.2019, p. 1035-1043.

    Research output: Contribution to journalArticleResearchpeer-review

    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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    U2 - 10.1038/s41588-019-0417-8

    DO - 10.1038/s41588-019-0417-8

    M3 - Article

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    Davies MR, McIntyre L, Mutreja A, Lacey JA, Lees JA, Towers RJ et al. Atlas of group A streptococcal vaccine candidates compiled using large-scale comparative genomics. Nature Genetics. 2019 Jun 1;51(6):1035-1043. https://doi.org/10.1038/s41588-019-0417-8