SBRI Teams With PATH To Pick Best Candidates for Malaria Vaccines

Xconomy Seattle — 

Seattle’s tight-knit global health community is getting a little tighter today. The Seattle Biomedical Research Institute (SBRI) has secured a $2.3 million grant from the PATH Malaria Vaccine Initiative to help sift through a load of discoveries it has made in recent years that researchers say could be critical ingredients in a more effective new vaccine.

The grant will be used to help SBRI scientists whittle down a list of 25 novel proteins on the malaria parasite, to see which ones have the greatest potential to become ingredients of a vaccine that would provoke a strong, protective immune system response. The goal will be to pick two to four of the most promising proteins over the next 18 to 24 months, and then start having serious talks with commercial partners in the biotech and pharmaceutical industry who can develop them further into practical products, says Ashley Birkett, director of preclinical research and development for the PATH Malaria Vaccine Initiative.

Malaria is one of the top priorities of the Seattle-based Bill & Melinda Gates Foundation, because the worst form of the parasite kills an estimated 1 million people a year in the developing world, mainly children. Scientists had reason to cheer late last year when a vaccine candidate from GlaxoSmithKline known as RTS,S was able to protect about 50 percent of the people tested in a large clinical trial, although that’s not nearly good enough to reach the Gates Foundation’s goal of eradicating malaria from the planet. The Glaxo vaccine is built with just one critical protein in the parasite, and by adding more novel proteins on the parasite (known as antigens) from SBRI, the Malaria Vaccine Initiative hopes to create a vaccine that raises the bar to 80 percent protection, Birkitt says.

“We need new targets, and SBRI has new targets,” Birkitt says.

An effective vaccine has eluded scientists for decades, partly because the deadly parasite, plasmodium falciparum, is a complex little organism for a bug, with 5,000 genes. Those numerous genes provide a moving target for scientists. The genes go through fluctuating on-off cycles when the parasite is living in mosquito saliva, and then its gene expression profile morphs when the parasite enters human blood. It goes through another transformation during about a 12-day period when the parasite enters the human liver, before it becomes more virulent in the blood, Birkett says. (SBRI’s Stefan Kappe explained some of the biology of a promising vaccine candidate in this story back in December.)

PATH’s Malaria Vaccine Initiative is one of the leading funnels for research around the world, having secured $168 million from the Gates Foundation in September. The malaria vaccine group, which has offices in Bethesda, MD as well as Seattle, chose to support SBRI’s work because it has assembled multiple scientific collaborators with understanding of genomics, proteomics, and immunology, Birkitt says. Essentially, SBRI has studied the genomic metamorphosis of the parasite so that it has gotten a bead on which genes make the critical antigens at a moment when the malaria parasite is vulnerable, in the liver. It’s possible that a new vaccine made up of a couple of these critical proteins could spark antibodies and killer T cells of the immune system to kill the parasite at that phase, before it makes people deathly ill, Birkitt says.

The research at SBRI involves collaborators at the Walter Reed Army Institute of Research and immunologist David Koelle of the University of Washington. The work has been financed by the Gates Foundation, the U.S. Department of Defense, and the Foundation for the National Institutes of Health/Grand Challenges in Global Health initiative.