Developed in the lab of Seattle BioMed’s Stefan Kappe, Ph.D. [1], a promising genetically attenuated parasite (GAP) malaria vaccine candidate has proven 100 percent protective, 100 percent of the time, in mouse studies. Through precise deletion of two key genes in the malaria parasite, Kappe and his team have developed a live vaccine that gives protection and yields accurate, reproducible results over time.
Minding the GAP
In the past, this approach to vaccine development – using a weakened form of the whole organism that causes a particular disease – has proven successful in eradicating smallpox, as well as controlling diseases such as flu and polio.
In 2010, Seattle BioMed moved the malaria GAP vaccine model "from mice to men" and began challenging humans with the vaccine at Walter Reed Army Institute of Research (WRAIR), a longtime collaborator with Seattle BioMed.
While subunit malaria vaccines have shown partially effective in clinical trials, the ability to use the entire parasite as a vaccine by weakening it through radiation has proven effective in decades past. Still the variability involved in the approach provides a challenge.
The Kappe lab has developed a vaccination strategy using early liver stage-arresting GAP. The validity of this approach has now been shown in Phase I human clinical studies, demonstrating that that human malaria parasite can be severely attenuated. But Kappe believes "we can do better."
New malaria research
Scientific research at Seattle BioMed is always focused on gaining new knowledge and putting that information immediately to use. New insights learned from initial human clinical trials of the GAP vaccine are enabling us to develop the next generation of broadly protective live-attenuated malaria vaccine candidates.
Seattle BioMed researchers, along with colleagues at the University of Iowa, reported research results that underscore the potential of late liver stage-arresting GAP, providing a powerful model for identifying antigens to generate protection, not only in the liver stage of the disease but also in the potentially deadly blood stage.
Next step in continuum
This next step in the scientific research continuum provides new knowledge that will be put to use in next generation vaccine candidate developments to provide even greater protection. "The ultimate goal is to develop a 'watertight' vaccine to provide full protection against malaria at the lowest possible dose," Kappe says. "We now have a very important piece of new information."
The new research shows (in a mouse model) that immunization with late liver stage-arresting GAP provided superior and long-lasting protection against liver-stage infection when compared with irradiated parasites or early liver-stage arresting GAP. This next generation of GAP is the best Seattle BioMed researchers have seen, largely because the diversity of protection is unmatched.