Genomics empowers vaccine makers to tackle shapeshifting bacteria

A pioneering genomic surveillance study has provided the clearest picture yet of the arms race between Streptococcus pneumoniae, the bacterium responsible for a range of illnesses such as pneumonia and meningitis, and the vaccines designed to protect against the most dominant types. A strain called GPSC10 was found to be a particular threat, due to its increased virulence, ability to transform its structure to evade vaccines and its resistance to several common antibiotics.

The study, published today (16 August) in Lancet Microbe, was led by the Wellcome Sanger Institute, National Reference Center for Pneumococci, France, and Hospital Sant Joan de Deu, Spain, as part of the Global Pneumococcal Sequencing (GPS) project. The findings demonstrate the value of genomic surveillance to inform vaccine design and highlight the challenge posed by ‘shapeshifting’ strains like GPSC10.

Streptococcus pneumoniae, also known as the pneumococcus, is a bacterial pathogen that causes diseases ranging from ear infections through to pneumonia, septicaemia and meningitis. It is responsible for around nine million global infections annually, with elderly adults and children particularly susceptible. More than 300,000 children die from pneumococcal infection each year, mainly in low- and middle-income countries (LMICs)1.

Since 2000, a series of pneumococcal conjugate vaccines (PCVs) have been deployed that have targeted S. pneumoniae serotypes responsible for most disease cases in infants2, resulting in a reduction in disease worldwide. Currently, PCV-13 targets 13 serotypes and PCVs targeting up to 25 serotypes are in development. However, there are more than 100 distinct serotypes, and they can affect children and adults in different ways. Knowing which serotypes to target with the PCVs, and what the likely impact will be on disease and the wider pneumococcal population, is vitally important when designing effective global vaccination strategies.

Through the work of the GPS project since 2011, a picture of the S. pneumoniae serotypes in circulation has been built up that allows trends in the bacterial population to be identified. One serotype, 24F, has been on the rise, as documented by the National Reference Center for Pneumococci, France and many other countries such as Canada, Denmark, Germany, Israel, Italy, Japan, Lebanon, Norway, Spain, and UK.

In this new study, scientists from the Wellcome Sanger Institute performed whole-genome sequencing on 419 samples of S. pneumoniae serotype 24F, collected from individuals in France between 2003 and 2018 by the National Reference Center for Pneumococci (NRCP) and Association Clinique et Therapeutique Infantile du Val-de-Marne (ACTIV), and on 91 pneumococcal serotype 24F isolates collected from individuals in Spain by the Hospital Sant Joan de Deu. To provide a global comparison, an international collection of other S. pneumoniae genomeswere added from the Global Pneumococcal Sequencing (GPS) project database.

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