Re: Lab Will Pay to Infect People With Malaria
Source:
http://seattlepi.nwsource.com/local/356022_malvax22.html?source=mypi
Volunteers lining up to be bit by mosquitoes carrying malaria
By TOM PAULSON
P-I REPORTER
In little more than five years, Seattle has become an international center for malaria vaccine research and, apparently, will have no trouble finding volunteers willing to get bit by malaria-infected mosquitoes bred in a lab on Westlake Avenue.
"I've had to stop answering my phone," said Dr. Patrick Duffy, chief of the malaria program at the Seattle Biomedical Research Institute. "This is a great place to do research."
Duffy and his colleagues, working with financial support from the Bill & Melinda Gates Foundation and in collaboration with the PATH Malaria Vaccine Initiative, are creating one of the world's few labs for conducting human tests of experimental malaria vaccines.
There are only three such labs today, at the Walter Reed Army Institute of Research in Maryland, at the University of Oxford and at the University of Nijmegen, the Netherlands.
When the plans were announced recently to begin doing human malaria vaccine trials here next summer, Seattle Biomedical got thousands of e-mails and countless telephone calls from people volunteering to get bitten by parasite-ridden skeeters for the sake of science.
"It was an amazing response," said Dr. Christian Loucq, director of the Malaria Vaccine Initiative. "We have eight candidate vaccines now and a long list of new ones coming up."
The initiative, based in Bethesda, Md., but operated by Seattle-based PATH, helps coordinate many experimental malaria vaccine trials worldwide. It was launched in 1999 with a $50 million grant from the Gates Foundation and has administered nearly $300 million in Gates grants so far to assist in the search for a malaria vaccine.
The Seattle malaria vaccine trial volunteers will be paid several thousand dollars. There is a pretty good chance that some of them will fall ill with malaria (to be followed, in such cases, by curative drug therapy) and perhaps help scientists finally identify an effective vaccine to combat one of the planet's biggest killers.
"All vaccines tested so far have failed to fully protect against the disease," said Dr. Stefan Kappe, a Seattle Biomedical scientist who hopes to test his own experimental vaccine in volunteers once the institute's "Human Challenge Center" gets up and running in 2009.
Kappe is taking an innovative approach to creating a vaccine. He and his team are tinkering with the parasite's genetics and breeding the altered bugs in lab mosquitoes to see if they can create a malaria parasite that is too weak to cause disease -- but enough like the normal, wild-type bug to stimulate an effective immune response.
"We discovered the genes responsible for blood-stage infection and we cut them out," Kappe said. The blood stage of the malaria infection, he noted, is what causes the most severe illness.
In mice, Kappe and his team have shown that when these genes are removed from the parasite, it fails to move into the blood from the liver and complete its life cycle.
"We believe it is a very promising approach," he said. Kappe said another organization, Bethesda-based Sanaria, is working on a similar approach using the whole parasite but weakening its infectivity by irradiating the bugs inside mosquitoes.
Nobody has yet worked out how to deliver a "vaccine" that is basically manufactured inside mosquitoes, but Sanaria also is trying to convert this bug-dependent lab methodology into something more amenable to typical pharmaceutical production and distribution methods.
While irradiating microbes to create weakened, or "attenuated," versions of the bug is a well-established approach to making a vaccine, Kappe said he is not sure Sanaria's approach will work as well for malaria.
"This is a very complex organism," he said. Unlike a typical virus or bacterium with maybe a dozen or even hundreds of genes, malaria has about 5,000 genes.
"We do know people can become immune," said Duffy, who before coming to launch the institute's malaria research program, worked at Walter Reed on pregnancy and malaria. But scientists still don't know exactly how the body learns to fend off the parasite, he said, and it will almost certainly take many years to identify, test and prove out a vaccine.
Dr. Regina Rabinovitch, head of the infectious diseases development program at the Gates Foundation, said the philanthropy is committed to eradicating malaria just as was done for smallpox.
But for the foreseeable future, Rabinovitch said, this will require a combination of approaches that include more aggressive prevention efforts using today's tools such as bed nets or anti-malarial drugs, improved drug treatments and a sustained scientific search for a vaccine.
Asked about recent criticism by other international health experts that the Seattle philanthropy exerts too much influence over the direction of malaria efforts worldwide, Rabinovitch said people are misreading the Gates Foundation's enthusiasm for certain projects -- like vaccine research -- as implicit disinterest or opposition to other ideas.
"This efforts requires collaboration since we can't fund everything," she said. The Gates Foundation has lent a lot of its credibility, and money, to promote greater interest and investment in the fight against malaria, she said.
"But that doesn't mean we're trying to set priorities for others," Rabinovitch said.
Seattle has become an epicenter for malaria vaccine research, and for many other global health enterprises, in large part because of the Gates Foundation, she acknowledged. The foundation has awarded more than $1.5 billion to malaria efforts.
But this is also partly because much of the biomedical talent was already here, she said, though struggling to find scraps of funding and support to work on these diseases of poor countries.
P-I reporter Tom Paulson can be reached at 206-448-8318 or
tompaulson@seattlepi.com.
Well, the malaria came back. He eventually recovered, but was very unhappy - they never asked his permission to perform this experiment on him. 
