Two-pronged immune response offers hope for effective Salmonella vaccine

January 25, 2010

Research from Malawi, Birmingham and Liverpool has renewed hope that an effective vaccine could be developed against nontyphoidal strains of Salmonella. The work, funded by the Wellcome Trust and GlaxoSmithKline, suggests that the body's immune system could be primed to tackle even the most resilient of strains.

In developed countries, nontyphoidal (NTS) are mainly food-borne and usually cause gastroenteritis. In rare cases, they can lead to bacteraemia (bacterial infections of the blood). However, in the , bacteraemia is far more common and serious: fatality rates can be as high as almost one in four among children under two years old and HIV-infected adults.

In previous research led by Dr Calman MacLennan, scientists based at the Malawi-Liverpool-Wellcome Trust Clinical Research Programme (MLW) in Blantyre, Malawi , showed that disease-causing strains of NTS were able to survive outside cells in the blood of children. This survival mechanism enables the bacteria to replicate unchecked, possibly leading to high levels of mortality associated with bacteraemia.

Dr MacLennan and colleagues also identified protective Salmonella-specific that develop in African children within the first two years of life, the period in which the majority of NTS-related cases of bacteraemia occur. These particular antibodies recognise the bacteria in the blood and then kill the bacteria without the help of . It is possible that these antibodies develop in response to a relatively mild infection by NTS or similar bacteria. Young children who have yet to encounter these bacteria lack the antibodies and are at greatest risk from infection.

However, the Salmonella bacteria can evade the antibodies by hiding away within phagocytes, another group of cells involved in the body's . Phagocytes ordinarily 'eat' invasive bacteria before destroying them, but the Salmonella bacteria have adapted to avoid being destroyed once inside the phagocytes.

In addition, some strains have become resistant to the killing effect of antibodies even when they are outside these cells. If the bacteria are not completely cleared from the body, then it is possible for infection to reoccur if a patient's immune system is compromised, for example through HIV infection.

"Nontyphoidal Salmonella is a very serious problem in Africa and we urgently need a ," says Dr MacLennan. "Our previous work gave some hope that a vaccine could be developed that produces antibodies to protect against fatal Salmonella infections. But unless we can develop a vaccine that completely clears the body of bacteria, including resistant strains, such a vaccine could quickly become redundant."

Today, the researchers from the University of Malawi College of Medicine, Liverpool School of Tropical Medicine and the University of Birmingham, publish a study in the Proceedings of the National Academy of Sciences, which demonstrates a second way that the immune system uses antibodies to kill the bacteria. The results are encouraging for the prospects of developing a vaccine, suggesting that a vaccine against NTS could be more effective than previously thought.

The research, carried out by Miss Esther Gondwe, a Malawian PhD student at MLW in Dr MacLennan's group, found that the bacteria could be tagged by the antibodies before being 'eaten' by the phagocytes. This made it more likely that the phagocytes would consume them, but would also flag them as unwanted guests, enabling the phagocytes to recognise and destroy them.

This two-pronged approach enables the to kill Salmonella bacteria both within and outside of the blood cells, enabling the body to rid itself of the bacteria including strains that are resistant to killing outside of cells. It further highlights the role that antibodies play in protecting people from Salmonella infection.

"Antibodies clearly play a very important role in protecting people from Salmonella infection," says Dr MacLennan. "This makes even stronger the case for developing a vaccine which can stimulate antibody production. Such a vaccine could potentially save the lives of thousands of African children who would otherwise die."

Dr MacLennan and colleagues will now look for the most effective antibodies for attacking the in the blood and for activating phagocytes to kill. Finding the best antibodies will be key to developing a much-needed vaccine.

More information: Gondwe EN et al. Importance of antibody and complement for oxidative burst and killing of invasive nontyphoidal Salmonella by blood cells in Africans. Published online in advance in PNAS; 25 January 2010.

Related Stories

Recommended for you

Tracing cell death pathway points to drug targets for brain damage, kidney injury, asthma

October 19, 2017
University of Pittsburgh scientists are unlocking the complexities of a recently discovered cell death process that plays a key role in health and disease, and new findings link their discovery to asthma, kidney injury and ...

Cancer drug found to offer promising results in treating sepsis in test mice

October 19, 2017
(Medical Xpress)—A combined team of researchers from China and the U.S. has found that a drug commonly used to treat lung cancer in humans offers a degree of protection against sepsis in test mice. In their paper published ...

Engineered protein treatment found to reduce obesity in mice, rats and primates

October 19, 2017
(Medical Xpress)—A team of researchers with pharmaceutical company Amgen Inc. report that an engineered version of a protein naturally found in the body caused test mice, rats and cynomolgus monkeys to lose weight. In their ...

New procedure enables cultivation of human brain sections in the petri dish

October 19, 2017
Researchers at the University of Tübingen have become the first to keep human brain tissue alive outside the body for several weeks. The researchers, headed by Dr. Niklas Schwarz, Dr. Henner Koch and Dr. Thomas Wuttke at ...

Inflammation trains the skin to heal faster

October 18, 2017
Scars may fade, but the skin remembers. New research from The Rockefeller University reveals that wounds or other harmful, inflammation-provoking experiences impart long-lasting memories to stem cells residing in the skin, ...

Large variety of microbial communities found to live along female reproductive tract

October 18, 2017
(Medical Xpress)—A large team of researchers from China (and one each from Norway and Denmark) has found that the female reproductive tract is host to a far richer microbial community than has been thought. In their paper ...

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

wiserd
not rated yet Jan 27, 2010
"It further highlights the role that antibodies play in protecting people from Salmonella infection...."Antibodies clearly play a very important role in protecting people from Salmonella infection," says Dr MacLennan."

What do lines like this really contribute to the story? Imagine if a story on a financial topic said "This highlights the importance of five dollar bills in buying things!" It was superfluous to say it once and they said it twice. Very inelegant, not to mention boring.

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.