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On Wednesday, Dr. Rafael Hernandez will roll up his sleeve and offer his forearm to 200 ravenous, malaria-infected mosquitoes.

If he’s lucky — and the Seattle scientists who cooked up the experiment are right — Hernandez won’t get sick. Nor should any of the nine other volunteers participating in early tests of a vaccine against malaria, a disease that kills a half-million people around the world every year.

“I’m not totally confident, but I think the risk is fairly low,” said Hernandez, a pediatrician and researcher at Seattle Children’s who decided to put himself on the line for the sake of malaria’s victims, particularly the African youngsters most at risk.

Even if the tests succeed, many hurdles remain before Seattle BioMed, the private research lab behind the effort, would have a commercially viable vaccine. But if all goes well, it’s possible a product could be on the market in less than 10 years, said project leader Stefan Kappe.

Kappe has already spent a decade at the lab in Seattle’s South Lake Union neighborhood pursuing an unusual vaccine strategy pioneered more than 30 years ago but abandoned because it was considered impractical.

It’s been a roller-coaster ride, starting with a $14 million grant from the Bill & Melinda Gates Foundation, then taking a stomach-churning plunge when a volunteer in an earlier trial came down with malaria.

When the Gates grant wasn’t renewed, the project stalled. A $3 million infusion from the U.S. Department of Defense finally put it back on track, allowing Kappe and his colleagues to develop an improved version that will face its moment of truth this month.

“I’m optimistic,” Kappe said. “I obviously believe this is the most promising way to make a malaria vaccine.”

The project’s initial Gates funding was part of an initiative to foster far-out ideas with the potential for big payoffs. Kappe’s approach certainly fit the bill.

It builds on work from the 1970s, when researchers zapped malaria-infected mosquitoes with radiation to weaken the parasites, then let the mosquitoes bite volunteers. The result was near-perfect immunity against the disease.

But it didn’t seem possible to vaccinate millions of people via mosquito bites.

Kappe took a slightly different tack. In his Seattle lab, he uses genetic-engineering techniques to snip out genes crucial to the parasite’s development. In theory, people bitten by mosquitoes carrying weakened parasites shouldn’t get malaria, and should become immune to the disease. But in the first human trials, one volunteer from a total of six came down with malaria.

So Kappe and his team went back to the drawing board and found a way to snip out additional genes. The upcoming trial will test whether they succeeded in creating truly toothless parasites, incapable of causing infection.

Hernandez and his fellow volunteers will expose their arms to a container full of mosquitoes for 10 minutes. Then it’s a waiting game.

The parasites incubate quietly inside a human host for a week or more before bursting out into the blood stream and triggering the classic malaria symptoms of fever, headache and chills.

Near the end of that incubation period, the volunteers will check into a hotel near Seattle BioMed where health workers will test their blood and monitor them for symptoms for 10 days. The volunteers will be paid about $1,800 each.

Seattle BioMed is one of only two labs in the nation certified to perform such trials. They rely on a strain of malaria that can be quickly cured with standard treatment. Multiple safeguards, including vaultlike doors and negative air pressure, prevent infected mosquitoes from escaping the facility.

To gain certification, the staff members at Seattle BioMed also had to prove they could infect people with malaria through mosquito bites. Tristan Victoroff, then a graduate student in public health at the University of Washington, volunteered for that first test in 2010 — knowing he was almost certain to get sick.

“I thought I could put up with a little discomfort to be involved in something pretty dynamic,” he recalled.

His first symptoms were a headache and overwhelming fatigue. “It feels like your head is full of sand and your motivation for even standing up is low.” He cycled through fever and chills so intense he shivered under a steaming shower.

But after a couple of days of treatment, Victoroff was fine. “I never felt so bad that I regretted it.”

This time around, Kappe will be going for long, calming runs while he waits to see what happens with this round of volunteers. If they are all healthy by the end of January, he and his team will celebrate — and plan their next steps.

Since the vaccine program was launched at Seattle BioMed, the use of bed nets and conventional drugs has cut the global malaria death rate nearly in half. The field is crowded with competing solutions to drive the numbers down even more, ranging from genetically engineered mosquitoes to simply scaling up methods that are already working.

The Seattle-based Gates Foundation is leading a push to eradicate the disease, but most experts believe that won’t be possible without an effective vaccine.

“Malaria is such a tenacious parasite,” Kappe said. “You can push it nearly to extinction, but if you don’t stamp it out completely, it will come back with a vengeance.”

Seattle BioMed’s vaccine strategy is only one of several in the pipeline. A more conventional approach, developed with Gates funding, is already nearing approval. But it doesn’t work very well, conferring only 30 to 50 percent protection.

“We have to think of unconventional strategies,” said Col. Peter Weina, chief of research programs at Walter Reed National Military Medical Center. ‘”That’s why I think the Seattle BioMed strategy has as good, or maybe even a better, chance of succeeding than what we’ve already tried.”

But practical obstacles remain to make a vaccine of whole parasites, which are larger and more complicated than the bacteria and viruses used in most vaccines, cautioned Ashley Birkett, director of the Gates-funded PATH Malaria Vaccine Initiative. That’s one reason it has proved so difficult to develop a vaccine against malaria or any other parasite.

If the new trial shows that Kappe and team have defanged the malaria parasite, they still have to show it can act as a vaccine and protect against infection, Birkett pointed out.

Then there’s the problem of how to deliver it. Right now, the researchers rely on mosquitoes to inject the weakened parasites into people. But wrangling mosquitoes on a large scale would not be practical.

The alternative is to mass produce parasites and formulate them into an injection. It’s been done on a small scale, but since the parasites can only complete their life cycle inside mosquitoes, it requires large colonies of the insects and painstaking extraction of the parasites.

“This is a whole new technological challenge,” Birkett said.

But if Kappe and his team show progress, there’s a chance PATH’s vaccine initiative — which has received nearly $700 million since its inception — will step in with additional funding, Birkett added.

As an expert in infectious disease himself, Hernandez knows the trial he’s participating in is an early step in a long process. But he’s hopeful it will have an impact.

“Hundreds of thousands of children still die from this disease, and I feel like we can do better,” he said.

Since the odds of getting malaria are slim, Hernandez said he’s not nervous. But he’s not looking forward to his date with the bloodsuckers.

“I’m afraid I will be pretty itchy the next day,” he said. “But it’s something I’m willing to concede as the cost of trying to figure out whether or not this vaccine is safe.”

Sandi Doughton at: 206-464-2491 or sdoughton@seattletimes.com