20/04/05

Cell suicide ‘is key to malaria vaccine’

The malaria parasite changes form during its life cycle Copyright: TDR / Wellcome Trust

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Researchers have found evidence that a promising malaria vaccine works by making infected liver cells commit suicide.


The malaria parasite changes form a number of times during its complex life cycle. After being injected into the human bloodstream when an infected mosquito bites, the parasites enter the liver in a form called sporozoites.


The parasites later move to the bloodstream where they reproduce and cause disease.


Attacking malaria while it is still in the liver is therefore seen as the most effective way to prevent infection and stop the parasite from being transmitted to other people.


Research has shown the human immune system will attack malaria sporozoites if it has previously been exposed to parasites that have been weakened by exposure to radiation.


Until now, scientists believed that this potential vaccine provoked an immune response because the parasite spent longer in the liver producing the molecules — known as ‘antigens’ — our immune systems use to recognise malaria.


But now a team of researchers led by Ana Rodriguez at the New York University School of Medicine, United States, has added to this explanation.


According to research they published this month (4 April) in The Journal of Infectious Diseases, liver cells infected with the weakened malaria parasites commit ‘cell suicide’ soon after infection.


This programmed cell death is a tactic our bodies use to destroy cells that are unwanted, damaged or are infected with a potentially harmful organism — thereby reducing the threat of disease.


Malaria parasites usually counteract this protective device. However, Eric James at the Medical University of South Carolina, United States and colleagues suggested last year that irradiated parasites might not be able to do so.


Rodriguez’s team confirmed James’s theory.


The cells that commit suicide are then engulfed by others that are part of the body’s immune system. These are therefore exposed to the parasite antigens, which enables the immune system to recognise and destroy malaria sporozoites in future.


James told SciDev.Net that although Rodriguez’s research confirms his theory, it does not “refute or conflict with” the earlier explanation that irradiation extends the time the antigens are produced by the parasite.


Stephen Hoffman, chief executive of Sanaria, a US company researching malaria vaccines, says the research gives useful insights into the way the immune response works.


He adds that while it is not conclusive proof of the cell death theory, it is certainly convincing evidence.


Hoffman’s company is investigating ways of making a malaria vaccine using parasites weakened by irradiation, and hopes to begin clinical trials of its safety and efficacy next year.


Reference:


The Journal of Infectious Diseases 191, 1576 (2005)