Genetic stability of pneumococcal isolates during 35 days of human experimental carriage

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Gladstone, R.A. ; Gritzfeld, J.F. ; Coupland, P. ; Gordon, S.B. ; Bentley, S.D. (2015)
  • Publisher: Elsevier BV
  • Journal: Vaccine, volume 33, issue 29, pages 3,342-3,345 (issn: 0264-410X, eissn: 1873-2518)
  • Related identifiers: pmc: PMC4503797, doi: 10.1016/j.vaccine.2015.05.021
  • Subject: Immunology and Microbiology(all) | Infectious Diseases | qw_805 | qw_806 | wc_20 | wc_217 | Pneumococcal vaccines | Article | Experimental human pneumococcal carriage | veterinary(all) | Vaccine efficacy against carriage (VEcol) | Molecular Medicine | Streptococcus pneumoniae | Public Health, Environmental and Occupational Health

Background\ud \ud Pneumococcal carriage is a reservoir for transmission and a precursor to pneumococcal disease. The experimental human pneumococcal carriage model provides a useful tool to aid vaccine licensure through the measurement of vaccine efficacy against carriage (VEcol). Documentation of the genetic stability of the experimental human pneumococcal carriage model is important to further strengthen confidence in its safety and conclusions, enabling it to further facilitate vaccine licensure through providing evidence of VEcol.\ud \ud Methods\ud \ud 229 isolates were sequenced from 10 volunteers in whom experimental human pneumococcal carriage was established, sampled over a period of 35 days. Multiple isolates from within a single volunteer at a single time provided a deep resolution for detecting variation. HiSeq data from the isolates were mapped against a PacBio reference of the inoculum to call variable sites.\ud \ud Results\ud \ud The observed variation between experimental carriage isolates was minimal with the maximum SNP distance between any isolate and the reference being 3 SNPs.\ud \ud Conclusion\ud \ud The low-level variation described provides evidence for the stability of the experimental human pneumococcal carriage model over 35 days, which can be reliably and confidently used to measure VEcol and aid future progression of pneumococcal vaccination.
  • References (22)
    22 references, page 1 of 3

    [1] Tocheva AS, Jefferies JM, Rubery H, Bennett J, Afimeke G, Garland J, et al. Declining serotype coverage of new pneumococcal conjugate vaccines relating to the carriage of Streptococcus pneumoniae in young children. Vaccine 2011;29:4400-4.

    [2] Melegaro A, Edmunds WJ. Cost-effectiveness analysis of pneumococcal conjugate vaccination in England and Wales. Vaccine 2004;22:4203-14.

    [3] Miller E, Andrews NJ, Waight PA, Slack MP, George RC. Herd immunity and serotype replacement 4 years after seven-valent pneumococcal conjugate vaccination in England and Wales: an observational cohort study. Lancet Infect Dis 2011;11:760-8.

    [4] Simell B, Auranen K, Kayhty H, Goldblatt D, Dagan R, O'Brien KL. The fundamental link between pneumococcal carriage and disease. Expert Rev Vaccines 2012;11:841-55.

    [5] Goldblatt D, Ramakrishnan M, O'Brien K. Using the impact of pneumococcal vaccines on nasopharyngeal carriage to aid licensing and vaccine implementation: a PneumoCarr meeting report March 27-28, 2012, Geneva. Vaccine 2013;32:146-52.

    [6] Gritzfeld JF, Cremers AJ, Ferwerda G, Ferreira DM, Kadioglu A, Hermans PW, et al. Density and duration of experimental human pneumococcal carriage. Clin Microbiol Infect 2014;20(12):O1145-51 (The Official Publication of the European Society of Clinical Microbiology and Infectious Diseases).

    [7] Gritzfeld JF, Wright AD, Collins AM, Pennington SH, Wright AK, Kadioglu A, et al. Experimental human pneumococcal carriage. J Visualized Exp: JoVE 2013. Issue 72.

    [8] Ferreira DM, Neill DR, Bangert M, Gritzfeld JF, Green N, Wright AK, et al. Controlled human infection and rechallenge with Streptococcus pneumoniae reveals the protective efficacy of carriage in healthy adults. Am J Respir Crit Care Med 2013;187:855-64.

    [9] Brueggemann AB, Griffiths DT, Meats E, Peto TE, Crook DW, Spratt BG. Clonal relationships between invasive and carriage Streptococcus pneumoniae and serotype- and clone-specific differences in invasive disease potential. J Infec Dis 2003;187:1424-32.

    [10] McCool TL, Cate TR, Moy G, Weiser JN. The immune response to pneumococcal proteins during experimental human carriage. J Exp Med 2002;195:359-65.

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