The post-vaccine microevolution of invasive Streptococcus pneumoniae.

Amelieke J H Cremers,Peter W M Hermans,Jacques F Meis,Marien I De Jonge,Sacha A F T Van Hijum,Stephen D Bentley,Aldert L Zomer,Gerben Ferwerda,Fredrick M Mobegi

doi:10.1038/srep14952

Abstract

The 7-valent pneumococcal conjugated vaccine (PCV7) has affected the genetic population of Streptococcus pneumoniae in pediatric carriage. Little is known however about pneumococcal population genomics in adult invasive pneumococcal disease (IPD) under vaccine pressure. We sequenced and serotyped 349 strains of S. pneumoniae isolated from IPD patients in Nijmegen between 2001 and 2011. Introduction of PCV7 in the Dutch National Immunization Program in 2006 preluded substantial alterations in the IPD population structure caused by serotype replacement. No evidence could be found for vaccine induced capsular switches. We observed that after a temporary bottleneck in gene diversity after the introduction of PCV7, the accessory gene pool re-expanded mainly by genes already circulating pre-PCV7. In the post-vaccine genomic population a number of genes changed frequency, certain genes became overrepresented in vaccine serotypes, while others shifted towards non-vaccine serotypes. Whether these dynamics in the invasive pneumococcal population have truly contributed to invasiveness and manifestations of disease remains to be further elucidated. We suggest the use of whole genome sequencing for surveillance of pneumococcal population dynamics that could give a prospect on the course of disease, facilitating effective prevention and management of IPD.

Highlights

The 7-valent pneumococcal conjugated vaccine (PCV7) has affected the genetic population of Streptococcus pneumoniae in pediatric carriage
The absolute increase in invasive pneumococcal disease (IPD) cases caused by non-PCV7 protected serotypes observed in the Netherlands[30], as well as within our cohort[31] is suggestive of serotype replacement or capsular switching
Despite serotype replacement in pneumococcal disease, after pediatric pneumococcal vaccination with PCV7 we observed a temporary bottleneck in gene diversity, which re-expanded mainly by genes already present in the original gene pool

Summary

Introduction

The 7-valent pneumococcal conjugated vaccine (PCV7) has affected the genetic population of Streptococcus pneumoniae in pediatric carriage. Immunization with a 7-valent pneumococcal conjugated vaccine (PCV), both in young children[2] and the elderly[3], has been demonstrated to be highly efficacious in preventing invasive pneumococcal disease (IPD) caused by vaccine serotypes. Since the introduction of routine pediatric immunization with PCV, several studies have detailed pneumococcal genomic epidemiology in pediatric carriage and otitis media under vaccine pressure. They all demonstrated that the pneumococcal genomic structure of pediatric carriage remained fairly stable, and that serotype replacement occurred mainly through expansion of previously existent clones[20,21,22,23,24,25]. The effect of pneumococcal vaccination on whole genome epidemiology of invasive pneumococcal disease remains unexplored, it may hold invaluable information on understanding the long term effects of mass vaccination, especially with regard to changes in clinical manifestation of disease due to the changing prevalence of virulence factors in the pneumococcal population

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Conclusion