More than 1.6 million people die every year from meningitis, blood poisoning (sepsis) and pneumonia caused by the bacterium Streptococcus pneumoniae. Dr Stuart Clarke, based in the School of Medicine, leads a team doing vital research on vaccines to protect us from these diseases.
Stuart’s team has been monitoring the performance of the pneumococcal conjugate vaccine (PCV7; Prevenar) that was introduced into the UK childhood immunisation schedule in 2006. They have been monitoring how the vaccine is performing by detecting any changes to the nature of Streptococcus pneumoniae bacteria, known as the pneumococcus, before and after the vaccine was introduced. Stuart, who holds the post of Clinical Senior Lecturer and Honorary Consultant in Health Protection, explains: “When a new vaccine is introduced, the concern is that it will exert a selection pressure on the bacteria. This means the strains of bacteria the vaccine protects against are replaced by those it doesn’t, so disease still spreads in spite of the vaccine. This is what we need to look out for.”
In 2006, Stuart’s team started a study to find out how these bacteria are being carried in the nose and throat (an area known as the nasopharynx) in the population, how they are changing and how these variations may have occurred. Funded by pharmaceutical company Pfizer (Wyeth), this is thought to be the only study of its kind to be carried out in the UK during the introduction of the pneumococcal conjugate vaccines. Stuart was awarded the Bupa Foundation award category of ‘best emerging medical researcher in the UK’ in 2009 for leading this world-class research.
A complex disease
The pneumococcus is an important cause of invasive pneumococcal disease (IPD), including meningitis, sepsis and pneumonia. It also causes minor infections such as middle ear infection (otitis media), mainly in children. IPD is a complex disease: there are at least 91 different types (known as serotypes) of pneumococcus, depending on the characteristics of the protective capsule that surrounds the bacterium, shielding it from our immune system. The pneumococcus can also swap DNA between its own species and other Streptococcus species, which allows it to survive, spread and become resistant to antibiotics. This has led to debate among medical professionals about the effectiveness of vaccines against the pneumococcus.
Using molecular surveillance techniques, Stuart’s team has monitored the epidemiology, or spread, of the different serotypes of pneumococcus in the population since 2001. “When the pneumococcal vaccine was licensed for infants and young children in the USA in 2000, we started monitoring the spread of pneumococcal bacteria, in preparation for the vaccine being introduced into the UK childhood immunisation schedule,” says Stuart.
The new vaccine, Prevenar, protects against seven serotypes of the pneumococcus and stops these from being carried in the nose and throat, in theory preventing them from being passed between people. By the time Prevenar was introduced into the UK childhood immunisation schedule in 2006, Stuart’s team had collected five years of valuable baseline data on the natural variations of the pneumococcal bacteria in the population. The results showed that even before the vaccine was introduced, there were fluctuations in the different serotypes of the pneumococcus circulating in the population.
Increasing public confidence
The pneumococcus can be carried in the nose and throat from an early age without causing any symptoms. Other studies have estimated that up to 40 per cent of people may be carriers of the pneumococcus, and could potentially be carrying IPD. The pneumococcus can enter the bloodstream from the nasopharynx to cause meningitis, sepsis or pneumonia.
The research supports pneumococcal vaccination policy and, importantly, the results give the public confidence that this is an effective vaccine for children. Stuart explains: “In theory, once the conjugate vaccine has been implemented in the childhood schedule, not only should it stop causing disease, but it should no longer be carried in the nose and throat.
“This is vital in nurseries and schools, where these types of bugs can be spread by close contact, just like a common cold. Then, someone who is vulnerable to the bacteria will get a serious illness such as meningitis, sepsis or pneumonia. If all the children are vaccinated against the pneumococcus, then the spread will be significantly reduced.”
Informing pandemic vaccine policy
Stuart’s research could also be valuable for informing vaccine policy in a pandemic. No one knows what effect a pandemic, such as the recent H1N1 swine flu, has on the other bacteria that people carry in their nose and throat. Stuart’s team hopes to do a large, community-based study to investigate the effects on the pneumococcus.
“We aim to look at how the pneumococcus is carried by people before, during and after a pandemic, over a three-year period,” Stuart explains. “There are still a lot of questions around the interactions between viruses and bacteria and the nose and throat – for example, which one comes first: is it the flu that comes first and you get pneumococcal pneumonia, or is the pneumococcus already there and it’s just waiting for the flu to come in and damage your respiratory tract to enable the pneumococcus to take effect?“
International partnerships
The team works in partnership with groups in Singapore and Kuala Lumpur in Malaysia. Stuart explains: “These countries have an interest in the pneumococcus and their vaccines aren’t yet freely available to the public. This means that they are provided on a private basis to people who can afford it – but many people can’t afford to have the vaccine.
“Our aim is to demonstrate that there is a real need for the vaccine to be added to the childhood schedule so everyone can access it. We will do this by improving the understanding of pneumococcal epidemiology in these countries using the same methods we’re using here in the UK,” says Stuart.
During small pilot studies in these countries, the team discovered new strains of pneumococcus that had not previously been described elsewhere in the world. “This finding shows that countries in South East Asia shouldn’t use data solely from the west to inform their vaccine policy. They may have different types of the bacteria and the impact of the vaccine programme may be different,”Stuart explains.
Through these partnerships, researchers at Southampton can better understand the epidemiology of the disease in South East Asia, and vice-versa. PhD students, both in Southampton and in the Far East, can gain valuable experience and training abroad.
Cross-disciplinary working
Stuart’s research is part of a broader collaboration with Dr Saul Faust, Director of the Wellcome Trust Clinical Research Facility and others in the School of Biological Sciences, the School of Engineering, and Southampton University Hospitals NHS Trust. Stuart’s research team includes senior scientist Dr Johanna Jefferies and two PhD students, Anna Tocheva and Rebecca Gladstone, both from the School of Medicine.
There are opportunities for undergraduate students to work in this area: each winter two fourth-year medical students join the team as part of their in-depth study. This summer, a student sponsored by the Nuffield Foundation will also be joining for a placement project. “We are supportive as a group in terms of training and we also have major collaborations across the School of Medicine and Biological Sciences, which give our members opportunities for multidisciplinary working,” says Stuart.
One important partnership involves a groundbreaking project on designing new vaccines to protect against the pneumococcus that has won funding from the Bill and Melinda Gates Foundation. The aim is to create vaccines to stop bacteria ‘ganging together’ and forming a defence layer, or ‘biofilm’, against antibiotics and the body’s immune system. By targeting these biofilms, the team hopes to reduce the mortality associated with meningitis and pneumonia.
The project is led by Dr Jeremy Webb from the School of Biological Sciences. Stuart’s team will be a key part of the project and will work alongside researchers from the universities of Liverpool and Bristol. Jeremy comments: “People often think of bacteria as single organisms, but in reality most bacteria cooperate to form complex communities.
“Vaccines in use today are generally based on the properties of single-celled bacteria. Our approach is new because we will target properties of the protective biofilms in order to design new vaccines.” Stuart emphasises how working at Southampton has given him a unique opportunity to work across teams. “We have the School of Medicine, a major teaching hospital, and also benefit from having the Health Protection Agency (HPA) regional microbiology laboratory downstairs from our laboratories. As I have a joint appointment between the University and the HPA, this provides excellent links for research in this field.” “There are very few other places – if any – in the country that could provide all the links needed for clinical research on microbiology relating to vaccines and epidemiology in the community.”
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