Genetically Modified Malaria Parasite "Could Lead to Vaccine"
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SciDev.Net (London)
December 7, 2004
Posted to the web December 7, 2004
Mike Shanahan
The first study showing that a live malaria parasite could one
day be used as a vaccine to protect people from the disease was
published yesterday (5 December).
By modifying the genes of a form of the parasite that causes ma-
laria in rodents, the researchers were able to prevent it from
moving from the rats' liver to their blood stream. Once in the
blood stream, the parasite normally enters red blood cells,
causing symptoms of disease. It is also from there that it can
be transmitted to others, through a new mosquito bite.
The researchers were able to trap the parasite in the liver by
'knocking out' one of the parasite's genes that earlier research
had suggested was important at the infective stage of the para-
site's life cycle.
The paper's lead author, Ann-Kristin Mueller of the Heidelberg
University School of Medicine, in Germany, told SciDev.Net the
study proves that, in principle, the deletion of a single gene
could be enough to create a form of the parasite that is unable
to affect human health.
Such a weakened parasite could be used as a vaccine by giving
the immune system a window of opportunity to develop the ability
to recognise and repel future infections of normal malaria para-
sites before they can pose threats to health.
To confirm the potential for this, Mueller and her colleagues
infected laboratory rats with normal malaria parasites after
first injecting them with the genetically modified version. They
found that the rats stayed healthy even when infected with
50,000 parasites two months after receiving the third of three
doses of modified parasites.
Mueller says the next step would be to target the same gene in
one of the human forms of malaria, and see how the human immune
system deals with the modified parasite. Also, she says it is
important scientists understand better the role of the deleted
gene.
The researchers are also looking at about 30 other rodent ma-
laria genes that also seem to be particularly important during
infection. They say the recent availability of complete genetic
maps of the malaria parasite should help develop a live vaccine
based on more precise genetic modifications.
"This is exciting work," says Sanjeev Krishna, a professor of
parasitology at St. George's Hospital Medical School in London.
"It proves the concept that a live parasite can be used as a
vaccine against malaria."
He adds, however that a human vaccine using the gene deletion
approach is still some way off. "Translating this into something
given to children - that takes time."
Krishna also warned that relying on a single deleted gene cre-
ates the risk that some of the modified parasites could overcome
the need for it and 'escape' from the liver to cause malaria.
It only takes one parasite to cause the disease," Krishna told
SciDev.Net.
Mueller's colleagues are based at the Heidelberg University
School of Medicine, Germany, the Seattle Biomedical Research In-
stitute, United States, and the University of Washington, also
in Seattle. Their research was partially funded by the Bill and
Melinda Gates Foundation and the US National Institutes of
Health.
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