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Clonal expansion within pneumococcal serotype 6C after use of seven-valent vaccine

Nicholas J Loman1, Rebecca A Gladstone, Chrystala Constantinidou

  • 1Centre for Systems Biology, School of Biosciences, University of Birmingham, Birmingham, United Kingdom.

Plos One
|June 1, 2013
PubMed

Insights

The seven-valent pneumococcal conjugate vaccine (PCV7) introduction led to increased Streptococcus pneumoniae serotype 6C carriage. Whole-genome sequencing revealed diverse lineages and vaccine-associated genetic changes.

Area of Science:

  • Microbiology
  • Genomics
  • Epidemiology

Background:

  • Streptococcus pneumoniae causes invasive pneumococcal disease, particularly in infants and the elderly.
  • The seven-valent pneumococcal conjugate vaccine (PCV7) reduced disease burden but led to serotype replacement.
  • An increase in serotype 6C carriage was observed following PCV7 introduction.

Purpose of the Study:

  • To investigate the genomic basis for the emergence of Streptococcus pneumoniae serotype 6C.
  • To analyze the genetic diversity and evolutionary dynamics of serotype 6C isolates.
  • To assess potential implications for future pneumococcal conjugate vaccine (PCV) development.

Main Methods:

  • Whole-genome sequencing of 19 Streptococcus pneumoniae serotype 6C isolates (15 carriage, 4 disease).
  • Phylogenetic network analysis to identify distinct lineages and clonal complexes.
  • Comparative genomic analysis of gene sets and sequences, focusing on capsular loci and surface protein genes.

Main Results:

  • Serotype 6C isolates belonged to four distinct phylogenetic lineages within a single geographical site.
  • Variations were identified in the 6C capsular locus and genes encoding surface proteins.
  • Independent capsular switching events introduced the 6C locus into multiple lineages, with rapid clonal expansion in one multi-locus sequence type (MLST) clonal complex 395 (CC395).

Conclusions:

  • The emergence of serotype 6C is driven by multiple capsular switching events and subsequent clonal expansion.
  • Genetic plasticity in vaccine-associated loci poses challenges for current and future pneumococcal conjugate vaccines.
  • Ongoing genomic surveillance and adaptive vaccine design are crucial for sustained protection against invasive pneumococcal disease.

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