August 14, 2002
(American Chemical Society) -- Researchers have
developed a unique vaccine that destroys a deadly
toxin produced by the parasite that causes
malaria, which kills more than two million people
each year. The vaccine appears extremely promising
in animal studies, they say.
If the drug works in humans, it could become a
more effective and longer lasting anti-malarial
vaccine than those currently available, according
to the researchers.
Details of the research will be presented next
week (Aug. 21) in Boston at the 224th national
meeting of the American Chemical Society, the
world's largest scientific society. The study will
be published in the Aug. 15 issue of Nature.
"This research represents an exciting new
approach to controlling malaria by blocking the
toxin that is responsible for so many deaths,"
says Peter H. Seeberger, Ph.D., associate
professor of chemistry at the Massachusetts
Institute of Technology in Cambridge, Mass. "We
hope that this is the answer, but we don't know
yet."
Tests of the new vaccine in monkeys are slated
to begin soon, while tests on humans could begin
within two years, said Seeberger, who is co-leader
of the study along with his colleague, Louis
Schofield, Ph.D., of the Walter & Eliza Hall
Institute of Medical Research in Melbourne,
Australia.
Although other vaccines have been developed and
tested against malaria, none lasts for more than a
few weeks. Most target proteins on the surface of
the parasite, which has the ability to change its
surface proteins and eventually resist the
vaccine, according to Seeberger.
The new vaccine targets the toxin instead of
the parasite. Although the parasite itself lives,
it is rendered harmless by the destruction of its
deadly toxin, he said.
One or two shots of the vaccine are expected to
provide lasting protection against the disease. If
necessary, its effectiveness could be enhanced by
using it in combination with other vaccines that
target the malarial parasite, Seeberger said.
Malaria is a life-threatening parasitic disease
transmitted by the bite of the female Anopheles
mosquito, which transfers deadly one-celled
parasites to human blood in an effort to nurture
her eggs. The disease can be caused by one of four
different parasites. The most lethal is
Plasmodium falciparum, which is also
responsible for the majority of infections.
Louis Schofield recently discovered that, as
part of its life cycle inside its human host, the
parasite releases an inflammatory toxin that
appears to trigger the fever, convulsions and
deaths associated with the disease.
Previous studies by Seeberger's colleagues
demonstrated that small amounts of the toxin - a
tiny carbohydrate molecule called GPI - could be
used to effectively immunize mice against
infection and reduce fatalities. But the human
immune system does not recognize such small
molecules as foreign and cannot make antibodies to
destroy them.
Seeberger and Schofield designed a synthetic
version of the toxin and attached it to a protein
molecule in hopes that the newly created complex
would be large enough for the body to recognize so
that an immune response could be launched against
it.
When a group of healthy, unvaccinated mice were
injected with blood containing a deadly malarial
parasite, all died. But when the synthetic toxin
was injected into a group of healthy mice and they
were subsequently injected with the parasite, 65
to 95 percent survived.
The immunized mice also had enhanced protection
from severe inflammatory conditions associated
with the disease, including swelling of the brain,
the researchers found.
Seeberger and his colleagues are continuing to
refine their vaccine formulations to achieve a 100
percent survival rate. They hope that similar
results will be seen in people.
According to the World Health Organization
(WHO), malaria is one of the major public health
problems, along with HIV/AIDS and tuberculosis, in
the poorest regions of the world. More than 90
percent of deaths from malaria occur in Africa,
mostly among infants and young children. It is
estimated that the disease kills one African child
every 30 seconds.
More recently, a dramatic surge in the number
of malaria cases occurring among U.S. travelers to
areas where the disease is common has been
reported.