Role of Antibodies Revealed in Body's Fight against Salmonella Infection
In developed countries, nontyphoidal salmonella (NTS) strains are mainly food-borne and usually cause gastroenteritis. In rare cases, they can lead to bacteraemia (bacterial infections of the blood). However, in the developing world, bacteraemia is far more common and serious: fatality rates amongst children under 2 years old can be as high as almost one in four and are even higher in HIV-infected adults.
"The problem of nontyphoidal salmonella in Africa is very serious, but has generally been overshadowed by the 'big three': malaria, HIV and TB," says Dr Calman MacLennan from the University of Birmingham who conducted this research whilst working at the Malawi-Liverpool-Wellcome Trust Clinical Research Programme in Blantyre, for the Universities of Liverpool and Malawi. "We have no human vaccines to protect against the disease and growing resistance to existing drugs means that a vaccine is now needed more than ever."
In research published today in the Journal of Clinical Investigation, Dr MacLennan and colleagues in Malawi and the UK have shown the important role played by antibodies in protecting against NTS. Previous work on salmonella has focused on cellular immune mechanisms rather than antibodies; this is because salmonella bacteria are able to survive within macrophages, a type of cell involved in the body's immune responses.
Dr MacLennan and colleagues found that disease-causing strains of NTS were able to survive outside cells in the blood of African children. They believe that the survival mechanisms which allow this to happen enable the bacteria to replicate unchecked and that this unrestricted growth may be responsible for the high levels of mortality associated with bacteraemia. The number of salmonella bacteria in the blood outside of cells can double every 20 minutes.
Most importantly, however, the researchers identified protective salmonella-specific antibody that develops in African children within the first two years of life, the period in which the majority of NTS-related cases of bacteraemia occur. This particular antibody is able to overcome the bacteria's protective mechanisms and kill them, ridding the blood of the infection. It is possible that these antibodies develop in response to a relatively mild infection by NTS or similar bacteria.
Dr MacLennan believes that the findings may prove important in the development of a vaccine against salmonella or a therapeutic to treat already infected children. A vaccine which triggers the body's immune system to generate the NTS-specific antibodies would enable the body to recognise and tackle the infection if it occurred.
"NTS have classically been thought of as intracellular pathogens, in other words, ones that survive in a person's cells, and that is where most vaccine efforts have been focused," says Dr MacLennan. "We have shown that in the blood of African children these bacteria can grow outside cells and so cause life-threatening bacteraemia, but in this location they can be tackled by antibodies. This is very important because successful vaccines are almost always those that produce antibodies."
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Notes for editors
MacLennan, C. A. et al. The neglected role of antibody in protection against bacteremia caused by nontyphoidal strains of Salmonella in African children. Published online in Journal of Clinical Investigation 20 March 2008.
The University of Birmingham
The University of Birmingham has around 27,000 students and 6,000 members of staff and a turnover of £360 million. Birmingham encompasses not only the lakeside setting and green landscape of its Edgbaston campus, but also has bases across Birmingham as well at the Shakespeare Institute in Stratford upon Avon and the Ironbridge Institute at the Ironbridge Gorge.
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