ROCKVILLE, Md., Sept. 8 /PRNewswire/ -- For malaria parasites to survive they must invade the red blood cells of humans. This red blood cell stage of the parasite life cycle is responsible for all of the 500 million cases and 1- 3 million deaths caused by malaria annually. Thus, a vaccine or drug that prevents invasion of red blood cells by the parasites would prevent survival of the parasite in humans and prevent death from malaria. 20 years ago it was established that a malaria protein called EBA-175 binds to the human red blood cell surface allowing the parasite to invade the red blood cells. By determining the molecular structure of EBA-175 researchers have uncovered valuable clues for rational anti-malaria vaccine and drug development. The findings were reported in the July 29, 2005 issue of the journal Cell. The recent efforts were co-led by Dr. Kim Lee Sim, President of Protein Potential LLC. Dr. Sim has worked for more than 15 years to develop this protein as a target for anti-malaria vaccines and drugs. After cloning the gene for EBA175, she identified the regions of EBA-175 involved with the binding of this protein to the red blood cell, discovered the regions on the red cell that bind EBA-175, and demonstrated that antibodies against this portion of EBA-175 prevent parasite invasion of red blood cells, and vaccines made from this protein protect monkeys against malaria. Recently Dr. Sim’s team at Protein Potential has worked as part of an effort sponsored by the NIH to manufacture an EBA-175 vaccine that will be tested in humans in the next year. The Protein Potential team developed the manufacturing methods and conducts key assays used to insure that the manufactured vaccine is potent and stable.
In the recently published paper, Dr. Sim and her collaborators at Cold Spring Harbor used X-ray crystallography to determine the atomic structure of a key portion of the EBA-175 protein called the region (R) II domain. Because RII binds on the red blood cell to glycophorin A, a protein with numerous sugar chains, the researchers determined the atomic structure of RII crystallized alone and with sugar molecules called glycans. The results showed that RII exists as a double molecule (dimer) bound together like two hands shaking and each dimer binds six glycans. This finding suggested that the RII handshake clamps the parasite protein onto glycophorin A on red blood cells, and blocking the RII handshake or interaction with glycophorin A -- with drugs or vaccines -- should reduce or prevent malaria infection.
Sim noted, “It has taken more than a decade since the discovery that region II of EBA-175 is critical to malaria parasite invasion of red blood cells to be able to visualize structurally how the process occurs. We hope this exciting finding will accelerate the development of interventions to reduce the more than one million deaths caused by malaria annually.”
Sim was joined in the study by Leemor Joshua-Tor, Niraj Tolia, and Eric Enemark of Cold Spring Harbor Laboratory.
Protein Potential’s Research and Development Group focuses on vaccine development. They have initiated internal programs to produce vaccines for SARS, dengue fever, tularemia, plague, and Plasmodium vivax malaria. Protein Potential’s Products and Services Group provides pharmaceutical and biotechnology companies, and government and academic institutions with high quality, recombinant proteins and DNA plasmids for research and development. Protein Potential also provides process development, documentation, and technological know-how to transition therapeutic, vaccine, and diagnostic proteins and DNA plasmids to large scale manufacture under cGMP conditions, and the validated assays required to release these proteins for clinical use. For more information see http://www.proteinpotential.com.
Contact: Robert C. Thompson Protein Potential LLC 9640 Medical Center Drive Rockville, MD 20850 Ph: (301) 770-3222 Fax: (301) 770-5554 Email: rcthompson@protpot.com
Protein Potential LLC
CONTACT: Robert C. Thompson of Protein Potential LLC, +1-301-770-3222,Fax: +1-301-770-5554, or rcthompson@protpot.com
Web site: http://www.proteinpotential.com/
