Try a killer Tropical

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Colorful killers. A new vaccine protects mice against parasites that cause leishmaniasis.

colorful killers. A new vaccine protects mice against the parasites that cause leishmaniasis.

Dennis Kunkel Microscopy Inc./Visuals Unlimited Inc.

A vaccine against leishmaniasis could save tens of thousands of lives each year. Now scientists say they used DNA extracts to stimulate the mice to fight against the parasites that cause the disease, an approach they hope to soon begin trials in people.

Leishmaniasis is caused by microscopic parasites of the genus Leishmania some 20 different species can sicken humans. Leishmaniasis hits the poor residents of the hardest tropical countries. Sandflies that spread the disease are silent and smaller than a mosquito. After the bite of a sand fly injects into the body, Leishmania cells can attack the skin or mucosa, causing ulcers or disfiguring lesions. In an often fatal form of the disease, they damage the liver, spleen and bone marrow. Although the outcome of the disease is uncertain, it is estimated that there are about 1.3 million new cases and up to 40,000 deaths each year.

Leishmania parasites are difficult enemies, and so far, no vaccine has received approval for use in humans. One challenge is that the parasites lay down inside of our cells, out of the reach of the antibodies elicited by most other vaccines. The key to the eradication of these invaders away, researchers suspect, stimulates immune cells called T cells Although leishmaniasis two experimental vaccines that use this strategy have undergone preliminary safety testing and efficacy in people the best method for the recruitment of T cells is unclear.

immunologist Peter Walden of Medicine Charité University in Berlin and his colleagues decided to try a DNA vaccine, a type of vaccine that is good to encourage T cell Such vaccines contain strands DNA encoding proteins from a pathogenic agent. The cells in the recipient's body absorb the vaccine DNA, and start churning out proteins-also called antigens, which alert the immune system and the first to attack if a true infection occurs.

First, the researchers had to choose the right antigens. They settled on five different proteins that vary little between Leishmania samples from a range of species found worldwide. To determine if the antigens galvanize human T cells, the team obtained blood samples from people in India and Tunisia who had recovered from the disease or were exposed to without getting sick. They found that parts of all five proteins have triggered a response by T cells of blood samples

mix final vaccine researchers, who tested in mice, contained five types of strands DNA, each coding for all or part of one of the proteins. The vaccine stimulated mice to produce defenses against parasites of leishmaniasis, Walden and his colleagues report online today in Science Translational Medicine . the cells of the vaccinated animals T responded vigorously to Leishmania antigens. To confirm that the vaccine has helped the animals to fight the invaders, the researchers injected the mice with cells of Leishmania species. Three weeks later, the mice that received the highest dose of vaccine made 94% fewer parasites in the liver than mice that received a control fail. Although some parasites remained in the mice that received the highest dose, Walden said there was not enough to cause disease symptoms.

"We are ready for human trials," he said. The vaccine must provide protection against different human Leishmania case, he adds, because the selected antigens are the same across species.

immunologist Paul Kaye of the University of York in the UK agrees that the time human trials came. "There is every reason to believe that they should go ahead as quickly as possible, "said Kaye, who was excited that there are now three vaccines to try in humans. Kaye and colleagues own candidate vaccine, which stimulates T cells with a harmless virus carrying sections of two Leishmania genes has already undergone a safety study in people, but the results are not not yet published.

"This is a significant advance," says Jesus Valenzuela vector biologist at the National Institute of Allergy and Infectious Diseases in Rockville, Maryland. Walden The group deserves help from human blood samples to identify antigens, he says, other vaccine developers have used rodents

leishmaniasis is one of the neglected tropical diseases for which research cash is difficult to obtain Yet Walden.. hope that he and his colleagues find funding for safety testing.

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