From the field
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Malaria research program uses multifaceted approach
By Theresa Raphael, Communications Officer, MVI
SEATTLE, Washington – This year promises to be a watershed year for malaria vaccine research at the Seattle Biomedical Research Institute (SBRI). Not only are SBRI scientists priming their first vaccine candidate to enter clinical trials at the Walter Reed Army Institute of Research (WRAIR), but funding from the PATH Malaria Vaccine Initiative has made possible the institute’s Malaria Clinical Trials Center—only the fourth site worldwide with the capacity to test malaria vaccines in humans—set to open later this year.
SBRI has established one of the most exciting malaria research programs in the United States, with close to 100 researchers focused only on malaria. Its multifaceted approach encompasses a genetically attenuated, whole-organism vaccine, a pre-erythrocytic antigen discovery program, and new vaccine evaluation methods.
Promising vaccine candidate in the wings
One promising aspect of SBRI’s malaria research program is a vaccine candidate that uses a genetically attenuated or weakened form of the whole malaria parasite. In this novel approach, Dr. Stefan Kappe, a principal investigator and senior scientist at SBRI, and his team identified and removed select genes from the malaria parasite—genes that are essential for the organism to thrive and replicate in the liver. As part of a vaccine, the weakened parasite remains in the liver, where it stimulates immune responses to other incoming malaria parasites, thereby preventing them from progressing to blood cells and causing malaria disease. Following successful results in mice, the emerging vaccine is set to move on to clinical trials in humans in 2009 at WRAIR, a partner in the project.
Focus on pregnant women
SBRI has also worked to identify antigens for use in a vaccine against malaria in pregnant women. With support from the Bill & Melinda Gates Foundation, Dr. Patrick Duffy—director of SBRI’s malaria program—and a consortium of laboratories have focused on assessing a limited number of parasite proteins as candidates for a vaccine that could be given before pregnancy to protect first-time mothers and their babies. Malaria infections during pregnancy are associated with maternal anemia as well as low birth-weight infants at greater risk of neonatal death. They are applying a similar strategy to develop a vaccine against a form of severe malaria that strikes children. To complement this effort, SBRI helped to establish a clinical research lab in Tanzania, where studies of malaria in pregnancy and severe malaria in children are underway.
Immunity to severe malaria in African children
Another international consortium led by SBRI is identifying the immune responses that protect African children from severe malaria. African children who survive one or two episodes of malaria typically develop resistance to the disease. Studies have shown that antibodies purified from the serum of immune, adult Africans could cure young children with malaria. The consortium is identifying the parasite forms and parasite proteins that may be targeted by protective antibodies, as a key step in developing vaccines to protect young children from severe malaria and death.
Novel malaria vaccine targets
Dr. Duffy has been collaborating with labs at WRAIR and the University of Washington and with the Kappe lab at SBRI to develop a vaccine that targets the parasite soon after its initial infection of a person—when it enters the human liver. Proteins expressed by liver-stage parasites may be used in vaccines to block malaria infection. MVI is funding SBRI research focused on prioritizing a panel of promising liver-stage antigens that could lead to identification of novel vaccine candidates to support its malaria vaccine portfolio.
For specific information on the collaboration between MVI, SBRI, and other partners follow the links below:
Project fact sheet:
- Accelerating the Quest for Malaria Vaccines by Expanding Capacity for "Human Challenge" Trials (511 KB PDF)
- New collaboration builds on recent malaria antigen discovery
26 February 2009 (20 KB PDF)
- PATH Malaria Vaccine Initiative, Seattle Biomedical Research Institute accelerate search for malaria vaccine by expanding "human challenge" tests
5 March 2008 (33 KB PDF)