A self-assembling nanoparticle designed by a UConn professor is the key component of a potent new malaria vaccine that is showing promise in early tests.
For years, scientists trying to develop a malaria vaccine have been stymied by the malaria parasite’s ability to transform itself and “hide” in the liver and red blood cells of an infected person to avoid detection by the immune system.
But a novel protein nanoparticle developed by Peter Burkhard, a professor in the Department of Molecular & Cell Biology, in collaboration with David Lanar, an infectious disease specialist with the Walter Reed Army Institute of Research, has shown to be effective at getting the immune system to attack the most lethal species of malaria parasite, Plasmodium falciparum, after it enters the body and before it has a chance to hide and aggressively spread.
The key to the vaccine’s success lies in the nanoparticle’s perfect icosahedral symmetry (think of the pattern on a soccer ball) and ability to carry on its surface up to 60 copies of the parasite’s protein. The proteins are arranged in a dense, carefully constructed cluster that the immune system perceives as a threat, prompting it to release large amounts of antibodies that can attack and kill the parasite.
In tests with mice, the vaccine was 90-100 percent effective in eradicating the Plasmodium falciparum parasite and maintaining long-term immunity over 15 months. That success rate is considerably higher than the reported success rate for RTS,S, the world’s most advanced malaria vaccine candidate currently undergoing phase 3 clinical trials, which is the last stage of testing before licensing.“Both vaccines are similar, it’s just that the density of the RTS,S protein displays is much lower than ours,” says Burkhard. “The homogeneity of our vaccine is much higher, which produces a stronger immune system response. That is why we are confident that ours will be an improvement.
“Every single protein chain that forms our particle displays one of the pathogen’s protein molecules that are recognized by the immune system,” adds Burkhard, an expert in structural biology affiliated with UConn’s Institute of Materials Science. “With RTS,S, only about 14 percent of the vaccine’s protein is from the malaria parasite. We are able to achieve our high density because of the design of the nanoparticle, which we control.”
The research was published in Malaria Journal in 2013.
The search for a malaria vaccine is one of the most important research projects in global public health. The disease is commonly transported through the bites of nighttime mosquitoes. Those infected suffer from severe fevers, chills, and a flu-like illness. In severe cases, malaria causes seizures, severe anemia, respiratory distress, and kidney failure. Each year, more than 200 million cases of malaria are reported worldwide. The World Health Organization estimated that 627,000 people died from malaria in 2012, many of them children living in sub-Saharan Africa.
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