Genetics study reveals how bacteria behind serious childhood disease evolve to evade vaccines

Genetics has provided surprising insights into why vaccines used in both the UK and US to combat serious childhood infections can eventually fail.  Scientists at the University of Oxford and at the Centres for Disease Control and Prevention in Atlanta investigated the results of an American vaccination programme against pneumococcus (Streptococcus pneumoniae), the bacteria responsible for diseases such as pneumonia and meningitis, and over a million deaths in young people across the world each year.

In 2000, the US introduced a pneumococcal vaccine which targeted seven different types of the pneumococcus bacteria.  The vaccine was extremely effective and had a dramatic effect on reducing disease amongst the age groups targeted.  The same vaccine was introduced in the UK in 2006 and was similarly successful.   Newer vaccines, targeting more types of pneumococcus, have subsequently been introduced in both countries.

Using the latest genomic techniques combined with epidemiology, the researchers found pneumococcus bacteria that were able to camouflage themselves from vaccines by swapping the region of their genome responsible for making their polysaccharide coating with the same region from a different pneumococcus serotype, not targeted by the vaccine.

"Imagine that each strain of the pneumococcus bacteria is a class of schoolchildren, all wearing the school uniform. If a boy steals from his corner shop, a policeman - in this case the vaccine - can easily identify which school he belongs to by looking at his uniform.  But if the boy swaps his sweater with a friend from another school, the policemen will no longer be able to recognise him and he can escape.  This is how the pneumococcus bacteria evade detection by the vaccine," explained Dr Rory Bowden, from the University of Oxford.

This exchange of genomic regions occurs during recombination, whereby one of the bacteria replaces a piece of its own DNA with a piece from another bacterial type.

Dr Bowden and colleagues also showed that during recombination the bacteria traded a number of other parts of the genome at the same time, a phenomenon never before observed in natural populations of pneumococcus.  This is of particular concern as recombination involving multiple fragments of DNA allows rapid simultaneous exchange of key regions of the genome, potentially allowing the quick development of antibiotic resistance.

"Understanding what makes a vaccine successful and what can cause it to fail is important. We should now be able to understand better what happens when a pneumococcal vaccine is introduced into a new population," said Peter Donnelly, Director of the Welcome Trust Centre for Human Genetics, and corresponding author on the study.

Reference: Tanya Golubchik, Angela B Brueggemann, Teresa Street, Robert E Gertz Jr, Chris C A Spencer, Thien Ho, Eleni Giannoulatou, Ruth Link-Gelles, Rosalind M Harding, Bernard Beall, Tim E A Peto, Matthew R Moore, Peter Donnelly, Derrick W Crook & Rory Bowden,  "Pneumococcal genome sequencing tracks a vaccine escape variant formed through a multi-fragment recombination event", Nature Genetics  doi:10.1038/ng.1072