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Putting It All Together for a Malaria Vaccine, Other Global Infectious Diseases

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It all comes together. The various research projects going on at the Seattle Biomedical Research Institute all have the same goal — to combat global infectious disease — but are coming at that goal from different directions and with different tools. "A multidisciplinary approach is, I think, even more powerful," says Ken Stuart, the president and director of the institute.

Using this multipronged approach, along with funding from the Bill and Melinda Gates Foundation, researchers at SBRI have developed a genetically attenuated vaccine for malaria. In rodents, that vaccine has been shown to be nearly 100 percent effective, and a human version of the vaccine will soon be entering clinical trials.

To develop this vaccine against the Plasmodium falciparum NF54 strain, which Stuart says is a well-characterized strain studied in the lab, the SBRI team used a combination of genetic and transcriptomic approaches. They scoured through the parasite's genes to determine which ones are turned on when it reaches the liver stage of its life cycle — which is when it first becomes entrenched in its human host. From studying about a hundred genes active at that stage, the researchers worked out which ones that, if knocked out, would prevent P. falciparum from completing its lifecycle. They then developed their attenuated version of P. falciparum without that integral gene for use as a vaccine.

In collaboration with the Walter Reed Army Institutes, SBRI researchers will be moving this vaccine into human clinical trials. Stuart adds that the human version of the vaccine will include two turned-off genes "for safety's sake."

"We think it's going to be a very effective vaccine, but one that's not cheap to produce," Stuart says. "Ultimately, we'll be able to use these clinical trials also to do exploration, understand the basis for immunity, and therefore identify what will be vaccine candidates that will be easier to produce."

At the same time, SBRI researchers are working to improve treatment for malaria — Stuart says that convergence is his "mantra." They are using comparative genomics to study P. falciparum and related parasites to discover novel drug targets.

Research at SBRI also focuses on HIV, tuberculosis, and trypanosome diseases with the same multi-faceted approach. "Infectious disease is a good model system for the next step for systems biology related to disease, compared to complicated chronic disease," Stuart says, adding that their approaches are deliberately not organism-specific so that down the line their methods may be applied to other biological questions.

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