The Quest for a Malaria Vaccine: SBRI’s Stefan Kappe Stares Down a Leading Candidate

Xconomy Seattle — 

If everything breaks right for Stefan Kappe‘s research, he’ll be able to tell the grandkids he played a leading role in wiping out malaria. It will probably take 10 years, if not longer. But this guy is clearly undaunted. On a Friday afternoon at his office at the Seattle Biomedical Research Institute (SBRI), the German scientist stared me down with an intensity that says he doesn’t have a minute to waste.

“We don’t have a vaccine,” Kappe said. “For nearly 100 years, people have tried. It’s one of the highest priorities in medicine, but we haven’t been accomplish it.”

Malaria kills more than 1 million people each year, making it one of the world’s leading killers, according to the Centers for Disease Control and Prevention. Most of those deaths are among young children in sub-Saharan Africa, yet this disease is on the top of the minds of some of Seattle’s leading biomedical researchers. Kappe is one of those people, and since he isn’t available to discuss his work at our inaugural Xconomy Forum on Thursday, I made sure to track him down in advance. He has a timely story. The vaccine candidate he’s been working on for years is being primed to enter its first clinical trial in the middle of 2009 at Walter Reed Army Institute of Research.

The state of the art in malaria vaccines right now isn’t much to write home about, Kappe says. A candidate from GlaxoSmithKline called RTS,S/AS01 is in the final stage of clinical studies in children in Africa, and has shown an ability to protect them about 50 percent of the time from developing clinical symptoms of malaria.

“That’s not enough,” he says. “That’s not enough to eradicate malaria. We need a vaccine that probably is 90 percent effective or more. It’s a high bar.”

So exactly how does Kappe plan to take on this challenge, and how is this any different from the long list of failures that precedes him?

First, we need to know a few basics about vaccines. There are the whole-killed variety of vaccines, in which an entire bug (like rabies) is killed, and all the hallmarks of the virus are injected to provoke the immune system. Then there are live-attenuated (weakened) vaccines, like the polio or flu vaccine, that usually stimulate the immune defenses a little more vigorously because it’s, well, alive. Then again, it offers a small chance of actually infecting you with the bug. Last, there are snippets of protein, or sub-units, that can be clipped out to give the immune system something specific to attack that can’t actually infect you.

The Glaxo vaccine candidate uses this single-sub-unit protein approach. Kappe isn’t optimistic about this being the answer for malaria, because the parasite is more complex than most bugs, with about 5,000 genes. Waving one hallmark protein like a flag in front of a bull isn’t probably going to do enough to spark a strong, multi-pronged immune response to the malaria invader, he says.

So, Kappe prefers the live-weakened flavor of vaccine. Studies that date back to the 1960s in volunteers, including prisoners, found … Next Page »

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