Two-pronged immune response offers hope for effective Salmonella vaccine

Jan 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.

Explore further: US scientists make embryonic stem cells from adult skin

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

Salmonella in garden birds responsive to antibiotics

Jun 02, 2008

Scientists at the University of Liverpool have found that Salmonella bacteria found in garden birds are sensitive to antibiotics, suggesting that the infection is unlike the bacteria found in livestock and humans.

Gastric ulcer bacteria turn immune defense inwards

Jan 25, 2010

Despite a strong response from our immune defence, the body is unable to rid itself of the bacterium Helicobacter pylori. One reason for this is that this bacterium encourages elements of the immune response to remain in tis ...

How HIV vaccine might have increased odds of infection

Nov 03, 2008

In September 2007, a phase II HIV-1 vaccine trial was abruptly halted when researchers found that the vaccine may have promoted, rather than prevented, HIV infection. A new study by a team of researchers at the Montpellier ...

Scientists Find Rare, Potent Antibody to HIV-1

Feb 23, 2009

(PhysOrg.com) -- Scientists at Duke University Medical Center have for the first time isolated an important antibody in human serum that could potentially play a key role in the design of an AIDS vaccine. The research appears ...

Recommended for you

Leeches help save woman's ear after pit bull mauling

10 hours ago

(HealthDay)—A pit bull attack in July 2013 left a 19-year-old woman with her left ear ripped from her head, leaving an open wound. After preserving the ear, the surgical team started with a reconnection ...

New pain relief targets discovered

22 hours ago

Scientists have identified new pain relief targets that could be used to provide relief from chemotherapy-induced pain. BBSRC-funded researchers at King's College London made the discovery when researching ...

User comments : 1

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.

More news stories

LinkedIn membership hits 300 million

The career-focused social network LinkedIn announced Friday it has 300 million members, with more than half the total outside the United States.

Magnitude-7.2 earthquake shakes Mexican capital

A powerful magnitude-7.2 earthquake shook central and southern Mexico on Friday, sending panicked people into the streets. Some walls cracked and fell, but there were no reports of major damage or casualties.

Sun emits a mid-level solar flare

The sun emitted a mid-level solar flare, peaking at 9:03 a.m. EDT on April 18, 2014, and NASA's Solar Dynamics Observatory captured images of the event. Solar flares are powerful bursts of radiation. Harmful ...