Skip directly to site content Skip directly to page options Skip directly to A-Z link Skip directly to A-Z link Skip directly to A-Z link
Volume 20, Number 2—February 2014

Seven-Valent Pneumococcal Conjugate Vaccine and Nasopharyngeal Microbiota in Healthy Children

Giske Biesbroek, Xinhui Wang1, Bart J.F. Keijser1, Rene M.J. Eijkemans, Krzysztof Trzciński, Nynke Y. Rots, Reinier H. Veenhoven2, Elisabeth A.M. Sanders, and Debby BogaertComments to Author 
Author affiliations: University Medical Center Utrecht, Utrecht, the Netherlands (G. Biesbroek, X. Wang, K. Trzciński, E.A.M. Sanders. D. Bogaert); TNO, Zeist, the Netherlands (G. Biesbroek, B.J.F. Keijser); Julius Center for Health Sciences and Primary Care, Utrecht (R.M.J. Eijkemans); Netherlands Vaccine Institute, Bilthoven, the Netherlands (N.Y. Rots); Spaarne Hospital, Hoofddorp, the Netherlands (R.H. Veenhoven)

Main Article

Figure 1

Weighted UniFrac analyses (23) of nasopharyngeal samples of children at 12 and 24 months of age vaccinated with 7-valent pneumococcal conjugate vaccine. Clustering of samples was based on evolutionary (phylogenetic) relatedness by using Weighted UniFrac analyses. Clustering is shown in a circle dendrogram. Each branch represents a sample and each adjacent histogram represents the relative abundance of the top 5 operational taxonomic units (OTUs) found in that sample. Differences in length of bra

Figure 1. Weighted UniFrac analyses (23) of nasopharyngeal samples of children at 12 and 24 months of age vaccinated with 7-valent pneumococcal conjugate vaccineClustering of samples was based on evolutionary (phylogenetic) relatedness by using Weighted UniFrac analysesClustering is shown in a circle dendrogramEach branch represents a sample and each adjacent histogram represents the relative abundance of the top 5 operational taxonomic units (OTUs) found in that sampleDifferences in length of branches among samples reflect their distance (i.e., dissimilarity) to each otherBranches of reference samples were collapsed and are represented by black trianglesSamples are mostly dominated by Moraxella, Streptococcus, and Haemophilus spp., or the combination of Dolosigranulum and Corynebacterium spp., which highly affects sample clustering by Weighted UniFracBranches are colored according to age of sampled children (purple = 12 months, green = 24 months)No clear clustering of samples by age was observed.

Main Article

  1. Rappuoli  R, Miller  HI, Falkow  S. Medicine. The intangible value of vaccination. Science. 2002;297:9379. DOIPubMedGoogle Scholar
  2. Centers for Disease Control and Prevention (CDC). Progress in introduction of pneumococcal conjugate vaccine— worldwide, 2000–2012. MMWR Morb Mortal Wkly Rep. 2013;62:30811 .PubMedGoogle Scholar
  3. Bogaert  D, Keijser  B, Huse  S, Rossen  J, Veenhoven  R, van Gils  E, Variability and diversity of nasopharyngeal microbiota in children: a metagenomic analysis. PLoS ONE. 2011;6:e17035. DOIPubMedGoogle Scholar
  4. Bogaert  D, de Groot  R, Hermans  PW. Streptococcus pneumoniae colonisation: the key to pneumococcal disease. Lancet Infect Dis. 2004;4:14454. DOIPubMedGoogle Scholar
  5. Spijkerman  J, van Gils  EJ, Veenhoven  RH, Hak  E, Yzerman  EP, van der Ende  A, Carriage of Streptococcus pneumoniae 3 years after start of vaccination program, the Netherlands. Emerg Infect Dis. 2011;17:58491 .PubMedGoogle Scholar
  6. Hanage  WP, Finkelstein  JA, Huang  SS, Pelton  SI, Stevenson  AE, Kleinman  K, Evidence that pneumococcal serotype replacement in Massachusetts following conjugate vaccination is now complete. Epidemics. 2010;2:80–4.
  7. Weinberger  DM, Malley  R, Lipsitch  M. Serotype replacement in disease after pneumococcal vaccination. Lancet. 2011;378:196273. DOIPubMedGoogle Scholar
  8. Spijkerman  J, Prevaes  SM, van Gils  EJ, Veenhoven  RH, Bruin  JP, Bogaert  D, Long-term effects of pneumococcal conjugate vaccine on nasopharyngeal carriage of S. pneumoniae, S. aureus, H. influenzae and M. catarrhalis. PLoS ONE. 2012;7:e39730. DOIPubMedGoogle Scholar
  9. Block  SL, Hedrick  J, Harrison  CJ, Tyler  R, Smith  A, Findlay  R, Community-wide vaccination with the heptavalent pneumococcal conjugate significantly alters the microbiology of acute otitis media. Pediatr Infect Dis J. 2004;23:82933. DOIPubMedGoogle Scholar
  10. Casey  JR, Pichichero  ME. Changes in frequency and pathogens causing acute otitis media in 1995–2003. Pediatr Infect Dis J. 2004;23:8248 . DOIPubMedGoogle Scholar
  11. Casey  JR, Adlowitz  DG, Pichichero  ME. New patterns in the otopathogens causing acute otitis media six to eight years after introduction of pneumococcal conjugate vaccine. Pediatr Infect Dis J. 2010;29:3049 .PubMedGoogle Scholar
  12. Faust  K, Sathirapongsasuti  JF, Izard  J, Segata  N, Gevers  D, Raes  J, Microbial co-occurrence relationships in the human microbiome. PLOS Comput Biol. 2012;8:e1002606. DOIPubMedGoogle Scholar
  13. Cho  I, Blaser  MJ. The human microbiome: at the interface of health and disease. Nat Rev Genet. 2012;13:26070 .PubMedGoogle Scholar
  14. Clemente  JC, Ursell  LK, Parfrey  LW, Knight  R. The impact of the gut microbiota on human health: an integrative view. Cell. 2012;148:125870. DOIPubMedGoogle Scholar
  15. van Gils  EJ, Veenhoven  RH, Hak  E, Rodenburg  GD, Bogaert  D, Ijzerman  EP, Effect of reduced-dose schedules with 7-valent pneumococcal conjugate vaccine on nasopharyngeal pneumococcal carriage in children: a randomized controlled trial. JAMA. 2009;302:15967. DOIPubMedGoogle Scholar
  16. Biesbroek  G, Sanders  EA, Roeselers  G, Wang  X, Caspers  MP, Trzciński  K, Deep sequencing analyses of low density microbial communities: working at the boundary of accurate microbiota detection. PLoS ONE. 2012;7:e32942. DOIPubMedGoogle Scholar
  17. van Gils  EJ, Veenhoven  RH, Rodenburg  GD, Hak  E, Sanders  EA. Effect of 7-valent pneumococcal conjugate vaccine on nasopharyngeal carriage with Haemophilus influenzae and Moraxella catarrhalis in a randomized controlled trial. Vaccine. 2011;29:75958. DOIPubMedGoogle Scholar
  18. van Gils  EJM, Hak  E, Veenhoven  RH, Rodenburg  GD, Bogaert  D, Bruin  JP, Effect of seven-valent pneumococcal conjugate vaccine on Staphylococcus aureus colonisation in a randomised controlled trial. PLoS ONE. 2011;6:e20229. DOIPubMedGoogle Scholar
  19. Schloss  PD, Westcott  SL, Ryabin  T, Hall  JR, Hartmann  M, Hollister  EB, Introducing mothur: open-source, platform-independent, community-supported software for describing and comparing microbial communities. Appl Environ Microbiol. 2009;75:753741. DOIPubMedGoogle Scholar
  20. Shendure  J, Ji  H. Next-generation DNA sequencing. Nat Biotechnol. 2008;26:113545. DOIPubMedGoogle Scholar
  21. Whitman  WB, Coleman  DC, Wiebe  WJ. Prokaryotes: the unseen majority. Proc Natl Acad Sci U S A. 1998;95:657883. DOIPubMedGoogle Scholar
  22. Cole  JR. The Ribosomal Database Project (RDP-II): previewing a new autoaligner that allows regular updates and the new prokaryotic taxonomy. Nucleic Acids Res. 2003;31:4423. DOIPubMedGoogle Scholar
  23. Lozupone  C, Knight  R. UniFrac: a new phylogenetic method for comparing microbial communities. Appl Environ Microbiol. 2005;71:822835. DOIPubMedGoogle Scholar
  24. Letunic  I, Bork  P. Interactive Tree Of Life (iTOL): an online tool for phylogenetic tree display and annotation. Bioinformatics. 2007;23:1278. DOIPubMedGoogle Scholar
  25. Cline  MS, Smoot  M, Cerami  E, Kuchinsky  A, Landys  N, Workman  C, Integration of biological networks and gene expression data using Cytoscape. Nat Protoc. 2007;2:236682. DOIPubMedGoogle Scholar
  26. van Gils  EJ, Veenhoven  RH, Hak  E, Rodenburg  GD, Keijzers  WC, Bogaert  D, Pneumococcal conjugate vaccination and nasopharyngeal acquisition of pneumococcal serotype 19A strains. JAMA. 2010;304:1099106. DOIPubMedGoogle Scholar
  27. Goslee  SC, Urban  DL. The ecodist package for dissimilarity-based analysis of ecological data. J Stat Softw. 2007;22:119.
  28. Crielaard  W, Zaura  E, Schuller  AA, Huse  SM, Montijn  RC, Keijser  BJ. Exploring the oral microbiota of children at various developmental stages of their dentition in the relation to their oral health. BMC Med Genomics. 2011;4:22. DOIPubMedGoogle Scholar
  29. Lemon  KP, Klepac-Ceraj  V, Schiffer  HK, Brodie  EL, Lynch  SV, Kolter  R. Comparative analyses of the bacterial microbiota of the human nostril and oropharynx. MBio. 2010;1:e0012910 .PubMedGoogle Scholar
  30. Tano  K, Olofsson  C, Grahn-Håkansson  E, Holm  SE. In vitro inhibition of S. pneumoniae, nontypable H. influenzae and M. catharralis by alpha-hemolytic streptococci from healthy children. Int J Pediatr Otorhinolaryngol. 1999;47:4956. DOIPubMedGoogle Scholar
  31. Laufer  AS, Metlay  JP, Gent  JF, Fennie  KP, Kong  Y, Pettigrew  MM. Microbial communities of the upper respiratory tract and otitis media in children. MBio. 2011;2:e0024510. DOIPubMedGoogle Scholar
  32. Frank  DN, Zhu  W, Sartor  RB, Li  E. Investigating the biological and clinical significance of human dysbioses. Trends Microbiol. 2011;19:42734. DOIPubMedGoogle Scholar
  33. Bogaert  D, van Belkum  A, Sluijter  M, Luijendijk  A, de Groot  R, Rümke  HC, Colonisation by Streptococcus pneumoniae and Staphylococcus aureus in healthy children. Lancet. 2004;363:18712. DOIPubMedGoogle Scholar
  34. Regev-Yochay  G, Dagan  R, Raz  M, Carmeli  Y, Shainberg  B, Derazne  E, Association between carriage of Streptococcus pneumoniae and Staphylococcus aureus in Children. JAMA. 2004;292:71620. DOIPubMedGoogle Scholar
  35. Cobey  S, Lipsitch  M. Pathogen diversity and hidden regimes of apparent competition. Am Nat. 2013;181:1224. DOIPubMedGoogle Scholar
  36. Lysenko  ES, Ratner  AJ, Nelson  AL, Weiser  JN. The role of innate immune responses in the outcome of interspecies competition for colonization of mucosal surfaces. PLoS Pathog. 2005;1:e1. DOIPubMedGoogle Scholar
  37. Xu  Q, Almudervar  A, Casey  JR, Pichichero  ME. Nasopharyngeal bacterial interactions in children. Emerg Infect Dis. 2012;18:173845. DOIPubMedGoogle Scholar
  38. Veenhoven  R, Bogaert  D, Uiterwaal  C, Brouwer  C, Kiezebrink  H, Bruin  J, Effect of conjugate pneumococcal vaccine followed by polysaccharide pneumococcal vaccine on recurrent acute otitis media: a randomised study. Lancet. 2003;361:218995. DOIPubMedGoogle Scholar
  39. Eskola  J, Kilpi  T, Palmu  A, Jokinen  J, Haapakoski  J, Herva  E, Efficacy of a pneumococcal conjugate vaccine against acute otitis media. N Engl J Med. 2001;344:4039. DOIPubMedGoogle Scholar
  40. Coker  TR, Chan  LS, Newberry  SJ, Limbos  MA, Suttorp  MJ, Shekelle  PG, Diagnosis, microbial epidemiology, and antibiotic treatment of acute otitis media in children: a systematic review. JAMA. 2010;304:21619. DOIPubMedGoogle Scholar

Main Article

1These authors contributed equally to this article.


Page created: January 17, 2014
Page updated: January 17, 2014
Page reviewed: January 17, 2014
The conclusions, findings, and opinions expressed by authors contributing to this journal do not necessarily reflect the official position of the U.S. Department of Health and Human Services, the Public Health Service, the Centers for Disease Control and Prevention, or the authors' affiliated institutions. Use of trade names is for identification only and does not imply endorsement by any of the groups named above.