Human trials to begin on genetically-engineered malaria vaccine

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A female Anopheles albimanus mosquito - a vector of malaria, predominantly in Central America (Photo: James Gathany)

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There were 247 million cases of malaria and 881,000 deaths worldwide from the disease in 2006, making it one of the world’s most common infectious diseases and an enormous public health problem, particularly in poverty stricken areas. We’ve previously looked at various proposals to fight the disease, from targeting the mosquitoes that spread it, to research into a possible vaccine. Now researchers at the Walter and Eliza Hall Institute in Melbourne, Australia, working in collaboration with researchers from the US, Japan and Canada, have renewed hopes by creating a weakened strain of the malaria parasite that will be used as a live vaccine against the disease. Human trials will begin in 2010.

To develop the vaccine the research team deleted two key genes in the Plasmodium falciparum parasite – which causes the form of malaria most deadly to humans. By removing the genes the malaria parasite is halted during its liver infection phase, preventing it from spreading to the blood stream where it can cause severe disease and death. This approach to vaccine development of using a weakened form of the whole organism that causes a particular disease has already proven successful in eradicating smallpox and controlling diseases such as flu and polio.

Professor Alan Cowman, head of the Walter and Eliza Hall Institute's Infection and Immunity division, said similar vaccines had been tested in mice and offered 100 percent protection against malaria infection. He said it was hoped the vaccine would produce similar results in humans. "Although two genes have been deleted the parasite is still alive and able to stimulate the body's protective immune system to recognize and destroy incoming mosquito-transmitted deadly parasites."

In developing the vaccine the researchers used knowledge from several decades ago when scientists proved that irradiated malaria parasites provide protection against subsequent malaria infection in animal models and humans.

"Although vaccines are under development that use whole malaria parasites weakened by irradiation to protect against infection, their safety and effectiveness rely on a precise irradiation dose and trial results have been variable," Professor Cowman said. "We believe that our genetically-attenuated parasite approach provides a safe and reproducible way of developing a whole organism malaria vaccine."

Professor Cowman said it was unlikely the weakened parasites used in the vaccine would regain their potency as the genes had been deleted from the genome and could not be recreated by the parasite. "In addition, the 'one-two punch' approach of deleting two essential genes make it extremely unlikely that the attenuated parasite vaccine could restore its capacity to multiply and lead to disease," he said.

The research is supported by a USD$17 million, five-year grant from the Bill & Melinda Gates Foundation, which has stated the eradication of malaria as one of its primary goals. The human trials of the vaccine will take place at the Walter Reed Army Institute of Research in Maryland, US, from early 2010 and millions around the world will be hoping they prove successful.

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