Outsmarting the Smartie bug

Complete description of pneumococcal vaccine targets

New tools in the fight against pneumococci – the bugs targeted by vaccines recently announced by the Department of Health – are described by a team led by scientists from the Wellcome Trust Sanger Institute. They have put together a complete description of the targets of the vaccine that will help monitor the disease and provide new tools for rapid diagnosis.

Pneumococci (formal name Streptococcus pneumoniae) are widespread, causing non-invasive disease, such as ear and sinus infections, and rarer, invasive disease, such as pneumonia and meningitis. About one in three children each year has an ear infection, of which about one-third will be due to the pneumococcus. More significantly, invasive disease is a major cause of death: around 1 million people, mostly young children in developing countries, die each year.

The research, published online today in PLoS Genetics, shows how the target of the vaccines, called the polysaccharide capsule, has evolved and allows the researchers to determine functions of the genes involved. The polysaccharide capsule forms a sugary coat around the bacterium and changing the structure of the capsule can help it to fool our immune defence systems – like a Smartie changing its colour.

“The bug has a polysaccharide coat which can take any one of 90 different forms, known as serotypes,” said Stephen Bentley, leader of the project at the Wellcome Trust Sanger Institute. “The coat is essential for its ability to cause disease and its interaction with our immune system and some serotypes are more likely to be associated with disease.”

“The current vaccines provide excellent protection against pneumococcal disease, but only that caused by some of the 90 serotypes, and it is important that we keep a watch on the development of this organism. Our work in describing all known variants will help in that surveillance”

Two vaccines are available. The first, PCV, recognizes seven forms of the capsule and protects against 82% of infections in children under five years of age in the UK. This will soon be given to UK children under the age of two. A second, PPV, recognizes 23 capsule types and protects against 96% of the UK’s strains but is not effective in infants and is mainly used to protect the elderly.

S. pneumoniae usually lives harmlessly in the air passages and in the first year of life most people are likely to have ‘carried’ at least one strain. It is passed from person to person by sneezing and other aerosols. However, it occasionally passes from the airways to invade other tissues. This can lead to any one of a range of diseases including meningitis and infections of the sinuses, ear, lungs and blood. Why it switches to become invasive is not known.

The team sequenced all genes required to make all 90 forms of the capsule (more than 1,800,000 letters of genetic code), determined their function and studied their evolution. The work gives the most complete understanding of capsule production in any bacterial species.

The new vaccine will protect children from many of the most common serotypes but monitoring is needed to check whether other serotypes start to cause some disease. It is known that pneumococci can switch their capsular polysaccharide and so, if an invasive strain changes its coat to a form not recognised by the vaccine, it might start to become more prevalent and cause disease.

The catalogue of capsules from all known strains will help in the development of new techniques for monitoring changes in capsule type so researchers can look out for such capsule switching.

“The new vaccine that will be given to UK children is very effective at protecting against serious pneumococcal disease, but it does not protect against disease caused by the rarer serotypes,” said Brian Spratt, Professor of Microbiology at Imperial College and a co-author of the study. “The catalogue of capsular genes will help us develop better methods to monitor the effect of the vaccine and allow us to see if changes of capsular types or increased prevalence of the rarer serotypes result in any increase in disease by serotypes not included in the vaccine.

“We must always be vigilant to changes in the properties of microorganisms when we introduce new vaccines or antibiotics. This catalogue will help us to develop new tools to keep a check on the march of the pneumococcus and is also going to give us fascinating insights into the evolution of the amazing diversity of capsular genes that can be produced by this pathogen”

Researchers are at pains to point out that current vaccines are enormously successful and vaccination plays an essential in protecting all of us. The pneumococcal vaccines have been shown to be safe and very effective at preventing widespread infections and are expected to greatly reduce serious pneumococcal disease in UK children, as they already have done in the USA.

Current research, such as the capsule study described here, is intended to ensure we keep ahead of organisms such as S. pneumoniae.