Clonal Expansion within Pneumococcal Serotype 6C after Use of Seven-Valent Vaccine

Nicholas J. Loman, Rebecca A. Gladstone, Chrystala Constantinidou, Anna S. Tocheva, Johanna M.C. Jefferies, Saul N. Faust, Leigh O'Connor, Jacqueline Chan, Mark J. Pallen, Stuart C. Clarke

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

Abstract

Streptococcus pneumoniae causes invasive infections, primarily at the extremes of life. A seven-valent conjugate vaccine (PCV7) is used to protect against invasive pneumococcal disease in children. Within three years of PCV7 introduction, we observed a fourfold increase in serotype 6C carriage, predominantly due to a single clone. We determined the whole-genome sequences of nineteen S. pneumoniae serotype 6C isolates, from both carriage (n = 15) and disease (n = 4) states, to investigate the emergence of serotype 6C in our population, focusing on a single multi-locus sequence type (MLST) clonal complex 395 (CC395). A phylogenetic network was constructed to identify different lineages, followed by analysis of variability in gene sets and sequences. Serotype 6C isolates from this single geographical site fell into four broad phylogenetically distinct lineages. Variation was seen in the 6C capsular locus and in sequences of genes encoding surface proteins. The largest clonal complex was characterised by the presence of lantibiotic synthesis locus. In our population, the 6C capsular locus has been introduced into multiple lineages by independent capsular switching events. However, rapid clonal expansion has occurred within a single MLST clonal complex. Worryingly, plasticity exists within current and potential vaccine-associated loci, a consideration for future vaccine use, target selection and design.

Original languageEnglish
Article numbere64731
JournalPLoS ONE
Volume8
Issue number5
DOIs
Publication statusPublished - 28 May 2013
Externally publishedYes

Bibliographical note

Funding Information:
SCC currently receives unrestricted research funding from Pfizer Vaccines (previously Wyeth Vaccines). JMJ and SCC have received consulting fees from GlaxoSmithKline. SNF acts as principal investigator for clinical trials conducted on behalf of Southampton University Hospitals NHS Trust/University of Southampton that are sponsored by vaccine manufacturers but receives no personal payments from them. SNF has participated in advisory boards for vaccine manufacturers but receives no personal payments for this work. SNF, SCC and JMJ have received financial assistance from vaccine manufacturers to attend conferences. All grants and honoraria are paid into accounts within the respective NHS Trusts or Universities, or to independent charities. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.

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