Rhode Island Hospital researchers have discovered a protein that is essential for malaria-causing parasites to escape from inside red blood cells. Antibodies to this protein trap the parasite inside these red blood cells. This protein could lead to the development of a vaccine that would prevent the progression of Plasmodium falciparum malaria, which kills one child every 15 seconds each year in Sub-Saharan Africa and Southeast Asia, according to new research by Jonathan Kurtis, M.D., Ph.D., and colleagues, published in the May 23 issue of journal Science.
"This research really began in 2002 when our colleagues from the National Institutes of Health, led by Patrick Duffy and Michal Fried, enrolled a birth cohort of children in Tanzania," said Kurtis, director of the Center for International Health Research at Rhode Island Hospital, and the study's principal investigator. "Six years ago we began using these samples to identify novel vaccine candidates and now it's coming full circle. While a portion of this research was conducted in mice, the actual vaccine discovery experiments were performed using human samples, thus we believe the results will effectively translate to humans."
In the mouse experiments, researchers conducted five independent vaccine trials in which mice were vaccinated with the novel antigen, which they have designated as Schizont Egress Antigen-1 (PfSEA-1) or control. All mice were then challenged with malaria parasites. In all five experiments, vaccinated mice had lower levels of malaria parasites and survived longer than the unvaccinated mice.
"When my post-doctoral fellow Dipak Raj discovered that antibodies to this protein, PfSEA-1, effectively trapped the malaria-causing parasite within the red blood cells, it was truly a moment of discovery,'" Kurtis said. "Many researchers are trying to find ways to develop a malaria vaccine by preventing the parasite from entering the red blood cell, and here we found a way to block it from leaving the cell once it has entered. If it's trapped in the red blood cell, it can't go anywhere… it can't do any further damage."
The researcher then measured antibodies to PfSEA-1 in the entire Tanzanian birth cohort of 785 children. Surprisingly, among children with antibodies to PfSEA-1, there were zero cases of severe malaria. To generalize their results, researchers then went back to a serum bank they had collected from 140 children in Kenya in 1997. They found that individuals with antibodies to PfSEA-1 had 50 percent lower parasitemia than individuals without these antibodies during a high transmission season.
"We still have additional trials ahead of us, first in another animal model, but we hope to begin Phase I trials in humans very soon," Kurtis said. "Our findings support PfSEA-1 as a potential vaccine candidate, and we are confident that by partnering with our colleagues at the National Institutes of Health and other researchers focused on vaccines to prevent the parasites from entering red blood cells, we can approach the parasite from all angles, which could help us develop a truly effective vaccine to prevent this infectious disease that kills millions of children every year."
- DK Raj et al. Antibodies to PfSEA-1 block parasite egress from RBCs and protect against malaria infection. Science, May 2014 DOI: 10.1126/science.1254417
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