UW scientists are developing a malaria vaccine that may be accessible to the developing world.

Every year, 500 million become ill with malaria, said Malcolm Gardner, affiliate professor of pathobiology and researcher at Seattle Biomedical Research Institute (SBRI), who sequenced the malarial parasite's genome. Malaria is deadliest in children less than 5 years of age. Every 30 seconds, malaria kills a child in Africa, according to the Centers for Disease Control and Prevention Web site.

Many living in malaria-endemic regions cannot afford effective anti-malarial drugs, and the parasite has developed resistance to older, inexpensive drugs, said Stefan Kappe, affiliate professor of pathobiology also working at SBRI, who is developing the vaccine.

"It's a massive public health crisis," Gardner said.

Now, with funding from the National Institutes of Health and The Bill and Melinda Gates Foundation, Kappe and his colleagues have exploited the complex life cycle of the malarial parasite to genetically engineer a vaccine.

Plasmodium — the parasite that causes malaria — infects a person when an infected mosquito bites him or her. The parasites then travel through the bloodstream into the liver, where they infect liver cells and start to replicate, Gardner said.

"It's during that stage that the parasite goes through a massive amplification, from maybe one parasite infecting a liver cell to maybe 40,000 parasites in that liver cell," Gardner said.

During this incubation stage, infected people have no symptoms of the disease at all, but once the parasite bursts the liver cell and enters the bloodstream, it infects red blood cells and causes fever, chills, malaise and sometimes coma and death, Gardner said.

Kappe and his colleagues engineered a weakened strain of the parasite that can only grow in the liver.

"We take the parasite and do genetic engineering on it until we find genes that are only important for the liver infection," Kappe said. "Then we can create an attenuated parasite strain, or weakened strain, that is still alive and can get to the liver and establish infection, but it cannot continue to infect the bloodstream."

The body's immune system recognizes the parasite inside the liver and mounts an immune response. If an infected mosquito later bites a vaccinated person, his or her body would recognize and quickly clear the parasite, Kappe said.

The vaccine has already shown impressive results.

"We've shown in rodents that the vaccine is 100-percent protective," Kappe said. "In rodents who live only two years, we can protect them for half of their life."

Now the researchers must show that a new vaccine prototype is both safe and effective in humans. They have teamed up with the Walter Reed Army Institute of Research to conduct safety trials on about 10 American subjects, Kappe said. Trials are expected to begin in spring 2008.

Even if the vaccine does prove effective in humans, some logistical issues may hinder its widespread deployment. The live vaccine must be frozen in liquid nitrogen in order to work, an expensive process that may not be feasible in the developing world, Gardner said. Creating enough vaccine to protect people in malaria-endemic regions may also prove difficult, he added.

"The argument has always been, at least until recently, that the practical issues of raising so many infected mosquitoes would be really technically demanding and expensive," Gardner said. "There are some logistical issues, but they may not be as severe as people think."

Researchers are already working on techniques for scaling production of the vaccine, Gardner said. There is also a growing awareness that governments or global charities will have to heavily subsidize anti-malarial measures in order for them to help the poorest regions, Kappe said.

"The Gates Foundation is one of the major charities that supports these kinds of activities," Kappe said. "If there is an effective vaccine for people in sub-Saharan Africa, I think they are committed to getting it out there."

Reach columnist Tia Ghose news@thedaily.washington.edu.