Sand flies transmit a deadly parasite, and also spit. The parasite needs the spit--which suggests a new approach to a vaccine.
Leishmaniasis, a parasitic disease transmitted by sand flies, is not a scourge in the United States, but it is elsewhere. An estimated 12 million people worldwide are infected with Leishmania, the genus of protozoan parasites that cause the disease. Although some species of Leishmania produce no more than pimples, others are lethal: in the southern Sudan alone, for instance, leishmaniasis has killed as many as 100,000 people in the past decade, as villagers fleeing a civil war have taken refuge in forests that are sand-fly breeding grounds. A species of Leishmania found in the Amazon basin has been known to eat away the entire face of its victim, until he starves to death or suffocates, sometimes many years after the initial infection. In part because leishmaniasis takes so many different forms, researchers have been unable to develop an effective vaccine against it.
But now Richard Titus, a cellular immunologist at the Harvard School of Public Health, thinks he may have found the parasite’s Achilles’ heel. He and his co-workers, including José Ribeiro of the University of Arizona, have discovered that all species of Leishmania seem to depend for their survival on a particular protein in sand-fly saliva. The researchers have even produced a vaccine against the protein that offers protection against the parasite--at least to mice.
Sand flies, Titus explains, are more than just flying syringes for drawing blood. When a sand fly jabs a human, it dribbles saliva into the wound. The saliva contains a protein called erythema-inducing factor, or EIF, which dilates the blood vessels (an erythema is the red spot around a bug bite), as well as a second protein that keeps the blood from clotting. EIF itself also suppresses the human immune response that might otherwise disable both proteins. The benefit of all this to the sand fly is that it keeps the blood meal flowing freely.
A few years ago Titus showed that Leishmania benefits from sand- fly saliva too. In fact, the parasite can’t do without it. When Titus injected mice with parasites--but not with saliva--the mice emerged from the assault free of disease. Recently, Titus has found that the key to the parasite’s well-being is EIF. In protecting itself from an immune response, EIF protects the parasite too.
More precisely, it allows Leishmania to thrive inside macrophages, the scavenger cells that normally engulf and destroy foreign invaders. To do its job, a macrophage must release signal proteins that activate other immune cells (T cells), prompting them to secrete another signal protein (interferon), which tells the macrophage to kill the parasite inside it. EIF somehow prevents the macrophage from stimulating T cells, and also from making hydrogen peroxide and nitric oxide, the toxic molecules that would normally kill the parasite. Far from being destroyed, the parasite multiplies inside the macrophage. It then infects other macrophages.
Titus’s vaccine is designed to defeat the parasite by blocking the action of EIF. The vaccine consists simply of EIF itself, mutated so that it no longer has its immunosuppressive power. In a recent experiment, Titus injected the vaccine into mice and found that they produced antibodies against EIF. When he later injected them with parasites and sand-fly saliva, one out of every five mice developed no symptoms at all. The rest developed lesions that were half the size and contained one- twentieth the number of parasites found in unvaccinated animals. Considering that Titus had injected up to a million parasites into each mouse--10,000 times as many as a sand fly normally transmits--his vaccine was a great success.
Next he plans to test it in dogs and monkeys--and eventually, if all goes well, in humans. If we had circulating antibodies in our blood and in our skin, they would neutralize EIF as it entered our body, says Titus. That would be very bad news for the parasite. And the beauty of this is it doesn’t matter what form of Leishmania the sand fly is carrying- -you’re going to be resistant to it.
In the United States, Leishmania afflicts only people who caught it abroad--Gulf War veterans, for instance. But that doesn’t mean Titus’s research on insect saliva doesn’t have implications close to home. He has recently found that a protein in the spit of deer ticks also suppresses the human immune response. Deer ticks transmit Lyme disease.
