SEATTLE, WA, June 15, 2011 – In a study published this week in Cell Host & Microbe, researchers from Seattle BioMed and the University of Iowa report results that underscore the potential of late liver stagearresting genetically attenuated parasites (GAP) as broadly protective next-generation live-attenuated malaria vaccine candidates. The new study shows potential as a powerful model for identifying antigens to generate protection, not only in the liver stage of the disease but in the blood stage as well.

While subunit malaria vaccines have shown partial efficacy in clinical trials, the ability to use the entire parasite as a vaccine by weakening it through radiation has proven effective in decades past – but provides a challenge because of the variability involved in the approach. Stefan Kappe, Ph.D., director of Seattle BioMed’s malaria research program, has previusly developed a vaccination strategy using early liver stage-arresting genetically attenuated parasites. The validity of this approach (using two gene deletions) has been shown in Phase I human clinical studies, demonstrating that the human malaria parasite can be severely attenuated.

According to Kappe, this study is the next step in the scientific research continuum – providing 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,” he said. “This study provides us with a very important piece of new information.”

The study reports that, using mouse malaria models, researchers discovered that immunization with late liverstage arresting GAP provided superior and long-lasting protection against liver-stage infection when compared with irradiated parasites or early liver-stage arresting GAP. “Rather than dying right after they reach the liver as the early arresting stage GAP or irradiated parasites currently do, the late liver stage arresting GAP infects, grows significantly and then dies, expressing a broader array of new antigens,” Kappe explained. “This is the next generation of GAP – the best we’ve seen because the diversity of protection is unmatched.”

The late liver stage arresting GAP also provided protection at the critical blood stage of infection (when an infected human develops the classic symptoms of malaria) – and across different malaria parasite species. Protective Immunizations in this study were also achieved via intradermal or subcutaneous routes, as opposed to past studies, which utilized only intravenous routes.

“Collectively, our data indicates that late liver stage arresting GAP constitute a superior strategy,” stated Kappe and co-author John Harty of the University of Iowa. “This underscores the potential utility of late-arresting GAP as broadly protective second-generation live-attenuated malaria vaccine candidates, as well as a model to find new vaccine candidates that protect against infection in both the liver and the blood stages of the disease.”

ABOUT SEATTLE BIOMEDICAL RESEARCH INSTITUTE:
Seattle BioMed is the largest independent, non-profit organization in the U.S. focused solely on infectious disease research. Our research is the foundation for new drugs, vaccines and diagnostics that benefit those who need our help most: the 14 million who will otherwise die each year from infectious diseases, including malaria, HIV/AIDS and tuberculosis. Founded in 1976, Seattle BioMed has more than 360 staff members. By partnering with key collaborators around the globe, we strive to make discoveries that will save lives sooner. For more information, visit www.seattlebiomed.org.

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For more information, contact:

Lee Schoentrup
206.256.7440

Jennifer Mortensen
206.256.7220