A malaria vaccine that imitates the parasite's effects on the human immune system has shown promise in its first human tests. Although the vaccine is a long way from protecting people in malaria-endemic areas, scientists say the unusual approach is paying off.
The malaria parasite, one of the world's biggest killers, is a devilishly difficult target for vaccines. Its complex lifestyle and its large genome mean that it can easily evade most antibodies that vaccines prompt the body to produce. But people living in malaria-endemic areas do naturally what vaccine developers hope to induce with an injection: They gradually build up immunity to the disease. They still become infected with the parasite but suffer fewer bouts of fever or anemia, and the disease rarely kills them.
Pierre Druilhe at the Pasteur Institute in Paris and his colleagues wondered if that natural immunity might provide clues to a successful malaria vaccine. They repeated part of an old experiment--first published in 1961--that demonstrated that immune system proteins from a naturally immune person could cure a subject who had caught malaria for the first time. In work that has spanned more than a decade, the researchers analyzed blood from adults living in malarial regions of Africa and eventually traced the protection to antibodies against a previously unknown malaria parasite protein called MSP3. They then demonstrated that antibodies to MSP3 activate the immune system's cell-killing machinery, which can attack and kill the parasite. Most other vaccine trials have tried to use the malaria parasite--rather than the body's reaction against it--to find possible targets for vaccines.
In the November PLoS Medicine, the team reports the results of the first human tests of a vaccine based on the MSP3 protein. In adult volunteers who had never been exposed to malaria, the vaccine prompted the production of MSP3-reactive antibodies in 18 of 30 subjects who received a series of three injections over 4 months. The antibodies were able to trigger parasite-killing reactions in culture dishes as well as in mice with the parasite. Even more promising, most of the vaccine recipients continued to produce protective antibodies a year after receiving their last shot.
"We do not pretend that we have a vaccine," Druilhe says. "We have antibodies that have good biological activities." Still, MSP3 could play a key role in a combination vaccine that prompts several kinds of antibodies, says Brian Greenwood, a malaria expert at the London School of Hygiene and Tropical Medicine. Druilhe says planned trials of the MSP3 vaccine with adult volunteers in Burkina Faso have been delayed by red tape and slow funding, but he hopes to begin them sometime next year.
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