A DEADLY and disfiguring disease could be prevented by an ingenious vaccine
that attacks the spit of sandflies, rather than the parasites their saliva
carries.
In tropical and desert regions around the world, over a million people a year
develop leishmaniasis after being bitten by sandflies infected with the
single-celled Leishmania parasite. The symptoms range from fevers, skin and
throat ulcers to disfigurement and death. In the 1990s, 100,000 people died
during one epidemic in Sudan.
Yet there are still no vaccines available against Leishmania. A
conventional vaccine has had only modest success in human trials, and medical
researchers are eager to find more effective strategies.
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Now Jos茅 Ribeiro and his colleagues at the National Institute of
Allergy and Infectious Diseases near Washington DC have come up with a unique
one: instead of attacking the parasite, go for proteins in the saliva of the
tiny flies that help transmit the disease.
In over a decade of research, Ribeiro and his colleagues have shown that the
saliva of sandflies such as Phlebotomus papatasi helps the parasite
invade the human immune cells called macrophages that are its preferred hosts.
Chemicals in the saliva attract macrophages to the area a sandfly has bitten,
yet dampen the cells鈥 immune activity.
However, the researchers also found previous exposure to saliva seems to
protect animals from Leishmania infections. So the researchers decided
to track down the molecules responsible for this protective effect.
They screened several proteins from Phlebotomus saliva to see if an
immune reaction against them would also protect mice against Leishmania
major, which causes skin ulcers. A protein of unknown function, which they
call SP15, turned out to give dramatic protection. Vaccinated animals infected
with L. major suffered only minor skin lesions that cleared in a few
weeks. In contrast, unprotected animals developed persistent ulcers that
destroyed tissue.
It鈥檚 a 鈥渘ew and potentially exciting approach toward vaccination against
vector-borne pathogens鈥, says Steven Reed, chief scientific officer of Corixa of
Seattle, Washington, which is developing a conventional Leishmania
vaccine.
However, different versions of such a vaccine may be needed for different
parts of the world and sandfly species. But while the hunt for the first spit
protein took more than a decade, new candidates could be tracked down quickly.
鈥淭he molecular biology revolution means we can now find, sequence and analyse
these proteins in a few months,鈥 says Ribeiro. 鈥淚t鈥檚 the most amazing
迟丑颈苍驳.鈥
Human trials are still at least three years away, but his team is close to
testing a vaccine in dogs, which are natural reservoirs for the parasite, and in
monkeys.
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More at:
The Journal of Experimental Medicine (vol 194, p 331)