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Population genomics of post-vaccine changes in pneumococcal epidemiology

Nature Genetics volume 45, pages 656–663 (2013)Cite this article

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Abstract

Whole-genome sequencing of 616 asymptomatically carried Streptococcus pneumoniae isolates was used to study the impact of the 7-valent pneumococcal conjugate vaccine. Comparison of closely related isolates showed the role of transformation in facilitating capsule switching to non-vaccine serotypes and the emergence of drug resistance. However, such recombination was found to occur at significantly different rates across the species, and the evolution of the population was primarily driven by changes in the frequency of distinct genotypes extant before the introduction of the vaccine. These alterations resulted in little overall effect on accessory genome composition at the population level, contrasting with the decrease in pneumococcal disease rates after the vaccine's introduction.

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Figure 1: Structure of the pneumococcal population.
Figure 2: Dynamics of the carried pneumococcal population.
Figure 3: Serotype dynamics of SC9.
Figure 4: Alteration in COG frequency between 2001 and 2007.
Figure 5: Distribution of antibiotic resistance genes.
Figure 6: Changes in β-lactam resistance.
Figure 7: Geographic structure within the population.
Figure 8: Effect of host age on pneumococcal genotype.

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Acknowledgements

N.J.C. is funded by an AX A postdoctoral fellow award. Research reported in this publication was supported by the National Institute of Allergy and Infectious Diseases of the US National Institutes of Health (NIH) under award R01AI066304 and by Wellcome Trust grant 098051. We acknowledge the support of the Sanger Institute core sequencing and informatics teams and productive discussions at PERMAFROST workshops. The content is solely the responsibility of the authors and does not necessarily represent the official views of the US NIH.

Author information

Author notes

  1. Stephen D Bentley, William P Hanage and Marc Lipsitch: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Epidemiology, Center for Communicable Disease Dynamics, Harvard School of Public Health, Boston, Massachusetts, USA

    Nicholas J Croucher, Patrick K Mitchell, William P Hanage & Marc Lipsitch

  2. Pathogen Genomics, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK

    Nicholas J Croucher, Julian Parkhill & Stephen D Bentley

  3. Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, Massachusetts, USA

    Jonathan A Finkelstein & Grace M Lee

  4. Division of General Pediatrics, Boston Children's Hospital, Boston, Massachusetts, USA

    Jonathan A Finkelstein

  5. Maxwell Finland Laboratory for Infectious Diseases, Boston University Medical Center, Boston, Massachusetts, USA

    Stephen I Pelton

  6. Department of Laboratory Medicine, Boston Children's Hospital, Boston, Massachusetts, USA

    Grace M Lee

  7. Division of Infectious Diseases, Department of Medicine, Boston Children's Hospital, Boston, Massachusetts, USA

    Grace M Lee

  8. Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK

    Stephen D Bentley

  9. Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, USA

    Marc Lipsitch

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Contributions

M.L. and W.P.H. conceived the project. M.L., W.P.H., S.D.B., J.P. and J.A.F. supervised the project. N.J.C. and P.K.M. analyzed the data. S.I.P. and G.M.L. helped with interpretation of the data. All authors contributed to writing the manuscript.

Corresponding author

Correspondence to William P Hanage.

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Competing interests

S.I.P. has investigator-initiated grants from Merck and Pfizer and has consulted for GlaxoSmithKline, Merck, Pfizer and Novartis. W.P.H. has consulted for GlaxoSmithKline. M.L. has consulted for Pfizer and Novartis.

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Supplementary Figures 1–29, Supplementary Table 2 (PDF 3703 kb)

Supplementary Table 1

Epidemiological data associated with isolates and accession codes associated with data deposited in the European Nucleotide Archive (XLSX 130 kb)

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Croucher, N., Finkelstein, J., Pelton, S. et al. Population genomics of post-vaccine changes in pneumococcal epidemiology. Nat Genet 45, 656–663 (2013). https://doi.org/10.1038/ng.2625

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