Vaccine reduces pneumococcal disease but not bacterial population

Pre-existing bacterial strains fill the gaps made by the pneumococcal vaccine, but cause less disease

DOI: 10.1038/ng.2625
Structure of the pneumococcal population, revealing 15 sequence clusters corresponding to clades within the population tree, ranging in size from 10 to 98 isolates. A sixteenth group constitutes a polyphyletic cluster of the remaining low frequency genotypes.
For the first time, researchers have tracked changes in an entire bacterial population following the introduction of a vaccine. They discovered that incidence of disease substantially reduced but the bacterium population has, unexpectedly, remained largely unchanged.

The collaboration between the Wellcome Trust Sanger Institute and the Harvard School of Public Health sequenced the whole genomes of Streptococcus pneumoniae taken from clinical samples in the seven years after the introduction of a pneumococcus vaccine in the US in 2000. The findings reveal that introducing a bacterial vaccine produces a markedly different effect to viral vaccines. In contrast to flu, where the virus evolves to overcome vaccination, other pre-existing strains from the pneumococcus bacterial population fill the void produced by the vaccine. These strains are thought to be less invasive, explaining why disease incidence reduced, but bacterial population numbers and genetic diversity barely altered.

Pneumococcus colonises the human nasal passages where it normally has no detrimental effects. However, for reasons that are not fully understood, the bacteria can cause diseases such as pneumonia, bacteraemia and meningitis. In 2000, 14.5 million episodes of serious pneumococcal disease were estimated to occur, including about 826,000 deaths in children aged 0-5 years (World Health Organization). Since 2000, anti-pneumococcal vaccines have been introduced which have been successful in protecting against seven strains that are most associated with disease in the US.

“This study gives an unprecedented insight into the bacteria living and transmitting among us. We can characterize these bugs to an almost unimaginable degree of detail, and in so doing understand better what helps them survive even in the presence of an effective vaccine.”

Co-senior author William Hanage Associate Professor of Epidemiology at Harvard School of Public Health

The team sequenced the genomes of more than 600 pneumococcal carriage isolates collected in Massachusetts, US through the roll-out of the 7-valent pneumococcal vaccine. The results confirmed that the parts of the bacterial population targeted by the vaccine had almost disappeared, but were replaced by pre-existing, rarer strains. The genetic composition of the new population is very similar to the original one, except for a few genes that were directly affected by the vaccine. This small genetic alteration may be responsible for the large reduction disease rates.

“The widespread use of whole-genome sequencing will allow better surveillance of bacterial populations – even those that are genetically diverse – and improve understanding of their evolution. In this study, we were even able to see how quickly these bacteria transmit between different regions within Massachusetts and identify genes associated with bacteria in children of different ages.”

Marc Lipsitch Professor of Epidemiology at Harvard School of Public Health and co-senior author of the study

The team suggests that further focused sequencing programmes may prove crucial to the future control of this, and other, bacterial pathogens that use similar mechanisms to outsmart human control measures.

“In the near future, we will be able to monitor pathogen evolution in close to real-time. Just as we know that bacteria can acquire antibiotic resistance, we knew that pneumococcus could potentially evade the vaccine. This is a demonstration of how we can monitor the evolution of pneumococcus and the mechanisms at play, information which will be beneficial for vaccine strategists. If we can quickly and precisely trace the emergence of disease-causing bacteria, we may be able to better target interventions to limit the burden of disease.”

Professor Stephen Bentley Co-senior author from the Wellcome Trust Sanger Institute

More information


Research reported in this publication was supported by the National Institute of Allergy and Infectious Diseases of the US National Institutes of Health (NIH) and by the Wellcome Trust.

Participating Centres

  • Center for Communicable Disease Dynamics, Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.
  • Pathogen Genomics, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK.
  • Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, Massachusetts, USA.
  • Division of General Pediatrics, Boston Children’s Hospital, Boston, Massachusetts, USA.
  • Maxwell Finland Laboratory for Infectious Diseases, Boston University Medical Center, Boston, Massachusetts, USA.
  • Department of Laboratory Medicine, Boston Children’s Hospital, Boston, Massachusetts, USA.
  • Division of Infectious Diseases, Department of Medicine, Boston Children’s Hospital, Boston, Massachusetts, USA.
  • Department of Medicine, University of Cambridge, Addenbrooke’s Hospital, Cambridge, UK.
  • Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, USA.


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