Malaria is caused by a parasite that enters the human bloodstream, courtesy of a mosquito.
"A few parasites infect you, and they grow and produce thousands of daughter parasites. Those parasites are then released from the liver and start infecting red blood cells," explained Evelien Bunnik, PhD, associate professor in the Department of Microbiology, Immunology & Molecular Genetics, Joe R. and Teresa Lozano Long School of Medicine at the UT San Antonio Health Science Center.
"This is where bad stuff starts to happen," Bunnik added. "That’s when you start to get sick."
Malaria kills more than half a million people a year, most of them young children. There are vaccines, but they don't work very well. Bunnick said this parasite is a tricky opponent for vaccine researchers.
"It's such a crafty little parasite. It's so well adapted to surviving within a human body and transmitting from one person to the next, Bunnik said. "How can you make one vaccine that protects everyone against this parasite that has learned how to escape from our immune responses, and that can sort of shapeshift?"
Bunnik co-led a global research team tasked with finding an answer to those questions. Scientists from the United States, Denmark, Spain, Tanzania, and Uganda collaborated using their diverse skill sets and expertise, and they discovered that the malaria parasite has a vulnerability. It lies within one of the methods it uses to avoid the human immune system, according to Bunnik.
The malaria parasite tucks itself away inside red blood cells, but if these cells remain in the bloodstream, they will eventually be identified by the spleen and removed from circulation. That would be the end of the line for the parasite.
But the malaria parasite has developed a way to avoid that fate.
"It produces proteins that it puts on the surface of the red blood cell, and those proteins bind to the walls of our blood vessels," Bunnik says. "So instead of staying in circulation, your infected red blood cells are now sticking to the walls of your blood vessels, and the parasite is no longer filtered out in the spleen. So it allows the parasite to survive."
A vaccine targeting these proteins would not work, Bunnik said. "These proteins are highly, highly diverse." Immune system warriors like antibodies just can't keep up.
But what about that spot to which the proteins bind? That sticky spot that allows the red blood cells to attach to blood vessels? That doesn't change. Are there antibodies that would be effective in neutralizing malaria's virulence if they targeted that receptor? Could that be the parasite's Achilles heel?
Bunnik's team isolated two monoclonal antibodies that could bind to this site and ran tests to see if they had any effect on the parasite. "We saw that our antibodies were able to inhibit infected red blood cells from binding to the walls of our blood vessels," Bunnick said. "So the antibodies that we've isolated basically exploit that Achilles heel, that weakness of the protein, because they bind to exactly that site."
This suggests that these two monoclonal antibodies might be an excellent foundation for the development of an effective malaria vaccine. Bunnik said a good vaccine would bring scientists a big step closer to their ultimate goal, the eradication of the malaria parasite.
"We really need all the tools that we can get to ultimately get rid of this parasite," Bunnik said, "because that would be the ideal scenario, that we can completely get rid of malaria parasites."
Bunnik was a co-lead author of the study that explored this malaria vulnerability and whether certain monoclonal antibodies might exploit it. It was published on November 20, 2024, in Nature.
