December 22nd, 2006 06:46 EST
Experimental Malaria Vaccine Targets Mosquitoes, not People
Washington -- Researchers at the U.S. National Institutes of Health (NIH) have developed an experimental vaccine that theoretically could eliminate malaria from entire regions by killing the malaria parasite in an area's mosquitoes, rather than preventing or limiting malaria in vaccinated individuals.
The one-celled parasites that cause malaria in people are Plasmodium falciparum and three closely related species. Each parasite lives part of its life in humans and part in mosquitoes. The disease is transmitted to people in the bite of an Anopheles mosquito and can result in severe headache, high fever, chills and vomiting.
The vaccine, tested only in mice so far, would help a vaccinated person’s immune system eliminate the parasite directly from the digestive tract of a malaria-carrying mosquito, after the mosquito has fed on the person’s antibody-enhanced blood.
Unlike many vaccines, this one eliminates the parasite from mosquitoes rather than protecting a vaccinated person from the disease.
Although several kinds of malaria vaccines are in development and testing, none has yet been licensed for widespread use.
Scientists at the NIH National Institute of Child Health and Human Development, in partnership with researchers at the National Institute of Allergy and Infectious Diseases and the National Institute of Diabetes and Digestive and Kidney Diseases, developed the vaccine.
COMPLEX LIFE CYCLE
Of the four species of parasites that infect people, Plasmodium falciparum is responsible for most malaria deaths, especially in Africa. (See related article.)
In 2004, according to the World Health Organization, the worldwide incidence of malaria was about 300 million cases a year and 1.3 million deaths, mostly among African children.
Each parasite is distinct under the microscope and produces a different pattern of symptoms. Two or more species can live in the same area and infect a single person at the same time.
When an infected female Anopheles mosquito bites a person, she takes in blood. At the same time, she injects saliva into a person’s bloodstream that contains the infectious form of the parasite. Once a malaria parasite infects humans, it changes in form and size as it invades different cell types, including red blood cells and liver cells.
Inside a person, the thread-like parasite quickly invades a liver cell. There, over a week or two (depending on the species), each parasite releases thousands of daughter cells into the bloodstream, where they invade red blood cells and eat hemoglobin, the oxygen-carrying part of the blood.
In the red blood cells, the parasite cells go through another series of stages, and the infection continues until it is brought under control by medicine or the body’s immune defenses. The parasite can complete its life cycle through the mosquito because some of its cells that penetrate red blood cells change into reproductive cells that circulate in a person’s bloodstream.
When a blood-seeking female Anopheles bites a person who has parasite reproductive cells circulating in the bloodstream, she sucks up and fertilizes the reproductive cells, which embed themselves in the mosquito gut before migrating by the thousands to the mosquito’s saliva-producing glands. There, the cycle begins again when she bites her next victim.
According to the researchers, many experimental vaccines have been tried against the form of the parasite that lives in people but have been unsuccessful or have produced limited immunity.
The Plasmodium cells evade the human immune system by hiding in liver and blood cells, making them difficult to target with a vaccine.
In this work, the researchers described several strategies for using conjugate technology -- which joins or “conjugates” molecules the immune system has difficulty recognizing to molecules it easily recognizes -- to make an effective vaccine.
The vaccine targets a protein called Pfs25 that is found only on the surfaces of the parasite reproductive cells that embed themselves in the mosquito gut.
When injected into human volunteers, Pfs25 fails to generate enough antibodies to target the parasite. But primed by the conjugate vaccine, the immune system starts making antibodies -- immune proteins that target specific molecules. The antibodies then eliminate molecules that the immune system normally would fail to detect.
The research revealed that the antibodies could completely eliminate the parasite reproductive cells.
"With conjugate technology, NIH researchers have developed effective vaccines against such scourges as … meningitis and typhoid fever," said Dr. Elias Zerhouni, NIH director, in a December 18 statement.
"The experimental malaria vaccine,” he added, “shows great promise for combating a terrible disease that exacts a devastating toll on the world's children."
The study authors said Psv25H, a molecule similar to Pfs25, is found on the surface of proteins of another Plasmodium species that causes malaria, Plasmodium vivax. They wrote that the conjugate technology easily could be adapted to make a vaccine against Psv25H.
The full text of an article describing the work is available on the Proceedings of the National Academy of Sciences Web site.
Additional information about malaria is available on the NIAID Web site.
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