Pandemics & Infectious Diseases

Post-Doctoral Fellowships

United States

Population Genomics of Emerging Pneumococcal Clones in a Vaccinated Community

Dr. Nicholas Croucher is on the tracks of a mass-murderer: Streptococcus pneumoniae, a.k.a pneumococcus, a bacterium that is responsible for hundreds of thousands of deaths all over the world – 800,000 children died because of it in 2000. That year, 15 million people were also affected by one of the illnesses it causes: pneumonia, septicemia, meningitis or otitis. Many of these cases are now difficult to treat as certain « clones » of the bacteria have evolved antibiotic resistance, which led to the development of an anti-pneumococcal vaccine. However, the impact of the vaccine is highly sensitive to the changes it causes in the bacterial population. Dr. Croucher will use bacterial genome sequences to trace how some pneumococcal « clones » evaded the vaccine through mutation while others were replaced with previously unseen strains. Tracing the genetic changes in the population provides improved understanding of how bacteria respond to different treatments, and how future clinical interventions might better manage this important pathogen.

Understanding the cloning strategy of the enemy

Immunization Week: How do bacteria become resistant?
Interview by Olivier Monod, published on 21/04/2014 at 13:35

Bacteria can become resistant to vaccines, just like they can become resistant to antibiotics. Nicholas Croucher, a researcher at Harvard supported by the AXA Research Fund, explains how Streptococcus pneumoniae bypasses the vaccines designed to target it.

In French: Semaine de la vaccination: comment les bactéries deviennent résistantes

How long can it take for Streptococcus pneumoniae to adapt to the vaccine?
For the PCV7 vaccine, which I am working on, some resistant strains emerged two or three years after the vaccination campaign began. By sequencing the genomes, we discovered that the mutants already existed before the vaccination campaign, but they were very rare. The vaccine enabled them to spread.
This suggests that the emergence of clones that are resistant to the vaccine is quite rare and slow. However, we need to continue to monitor the bacterial population, as new variants that are not affected by the vaccine could emerge in the future.

How does the vaccine that you are working on against Streptococcus pneumoniae work?

The polysaccharide conjugate vaccines (PCV) that protect against Streptococcus pneumoniae are highly effective against certain strains that cause the disease. They protect both adults and children, which is a real breakthrough in the fight against Streptococcus pneumoniae: previous vaccines were only effective in adults.

However, there are over 90 different strains of “pneumococcal” bacteria. PCV7 protects against 7 of these. Some new vaccines can reach up to 13. The most aggressive and antibiotic-resistant strains are targeted.

How do the bacteria adapt to the vaccine?

Streptococcus pneumoniae have high genetic variability. They can therefore evolve rapidly by exchanging genes between individuals. This makes it difficult to target the entire population with a vaccine. The PCV7 vaccine, which I am working on, only protects against a fraction of Streptococcus pneumoniae. Therefore, some strains are “resistant” because they were never targeted by the vaccine. Also, the strains targeted by the vaccine can develop resistance through mutation in the same was as antibiotic resistance.

Can a disease that has been eradicated through a vaccination campaign come back?

If the bacteria responsible for the disease is eliminated, then no. But if a reservoir of microbes exists somewhere in the world, then it is possible for a resistant mutant to emerge and spread through air travel. That’s why international coordination of efforts in terms of health is critical.

The path to research

Nicholas Croucher became a researcher because of a deep interest in evolution. From there, studying the adaptation of bacteria to therapeutic treatments was the obvious path. “It’s the best way to observe evolution in measurable time.” Nicholas Croucher is a postdoctoral fellow at Harvard University. His vaccine research is supported by the AXA Research Fund.

To add or modify information on this page, please contact us at the following address:



Harvard University


United States



ORCID Open Researcher and Contributor ID, a unique and persistent identifier to researchers