In just a few weeks, the folks at Seattle Biomedical Research Institute will start gathering precious bits of evidence on whether they’ve discovered something truly valuable over the past nine years. The global health nonprofit is on the verge of starting its first human clinical trial of a malaria vaccine, which it hopes will someday have potential to prevent most of the 1 million deaths a year caused by that mosquito-borne pathogen.
The update came last night from researcher Stefan Kappe, one of the featured speakers during Seattle BioMed’s annual fundraiser at the Westin Hotel downtown. It would be way too early to declare this anything close to a victory over malaria. But Seattle BioMed founder Ken Stuart, noting that biology sometimes requires “small, imperceptible steps” on the path to real progress, said getting a malaria vaccine candidate to move from concept, through animal experiments, to human clinical trials, is “stunning.”
Here’s the background, for those of you just tuning in. We first wrote about this vaccine program in detail in December 2008. Seattle BioMed (don’t call it SBRI anymore, it’s been re-branded) has been hot on the heels of Big Pharma giant GlaxoSmithKline, which is in the last of three phases of clinical trials with a vaccine candidate. The Glaxo vaccine, RTS,S has shown an ability to protect about half of people from the parasite, which causes nasty anemia that can be fatal, especially for children in sub-Saharan Africa. Seattle BioMed isn’t satisfied with that amount of protection, and is shooting for a vaccine that offer 90 percent protection, Kappe has said.
This has quest has taken a little longer than Kappe had hoped. When I spoke with him in December 2008, he was aiming to start the clinical trial in mid-2009. It’s now looking like it will be more like the second quarter of 2010.
There are reasons, of course, why these things take a while. Seattle BioMed has developed a live, weakened form of the malaria parasite as the key ingredient in its vaccine candidate. This trial, posted already on clinicaltrials.gov, is designed to enroll 32 healthy volunteers at a single site, Walter Reed Army Institute of Research in Silver Spring, MD. They will be given five doses of vaccine, four weeks apart. And here’s the kicker—the vaccine will be “challenged” when the volunteers are exposed and bitten by mosquitos carrying real malaria. These people, obviously, are going to be monitored extremely carefully, and if the vaccine doesn’t appear to be protecting them right away, they will be given a drug to treat the malaria before it starts causing problems for the volunteers, Kappe says.
While this is the kind of rigorous experiment that scientists want to see, to determine whether a vaccine works, it’s also got to go through time-consuming ethics review, and FDA scrutiny before it can start. “We’re injecting a live attenuated parasite, so FDA is looking very carefully at safety,” Kappe says.
The first batches of data to suggest whether the vaccine is safe ought to be available within five months, Kappe says. After about a year, researchers should have good data on how well it protects people from malaria, he says.
But that’s really only the beginning of the story. Seattle BioMed is already thinking about a second-generation formulation of the vaccine that would be more practical, designed to provide the longest-lasting possible protection at the lowest possible dose. Once it can make that new vaccine in accordance with the FDA’s consistent, sterile “good manufacturing practices,” then it will have to move on to much bigger trials of people in Africa, where the vaccine would have the greatest impact. Protection will really only matter if it can be shown to last for many years, Kappe says.
Actually manufacturing, marketing, and delivering the vaccine as a product is the stuff that companies do, not nonprofit research institutes, so at some point a partner will have to get involved. But last night, in a roomful of global health boosters, there was no shortage of can-do optimism.
“The animal studies say our vaccine should protect completely and for a long time,” Kappe says. But as he wisely pointed out, “human beings are not the same.”
