Dancing with the Enemy

Christen Brownlee

September 1, 2011

Dancing with the Enemy

The malaria parasite’s life cycle relies on humans and mosquitoes. Could we use the mosquito to stop the parasite?

Toward a Transmission-Blocking Vaccine

In contrast, Rhoel Dinglasan, PhD, MMI assistant professor, has developed a unique strategy with an intervention that isn’t administered directly to mosquitoes. Instead, it targets mosquitoes indirectly through their food source: humans. He’s creating a new vaccine that imbues mosquitoes with malaria-fighting power through antibodies in human blood. One blood snack would lead to Plasmodium protection for the insects, as well as protection for the next person that a mosquito bites.

Dinglasan’s vaccine isn’t the only “transmission-blocking” vaccine in development. Several research groups, including one led by former JHMRI Professor Nirbhay Kumar, PhD, have worked on similar approaches for decades. However, Dinglasan’s methodology has quickly gained the backing of the malaria community, including the PATH Malaria Vaccine Initiative, which funds other promising malaria vaccine initiatives. The recent stir over Dinglasan’s work is due to its unique success in attacking the two most common human malaria parasite species in all the species of mosquitoes tested thus far.

While completing his PhD, Dinglasan had become interested in the various naturally occurring sugars that attach to proteins present throughout mosquitoes—sugar-coated proteins known as glycoproteins. At the time, little was known about these glycoproteins. However, previous research had shown that glycoproteins in the mosquito’s midgut in particular appear to play a key role in Plasmodium’s ability to invade mosquito cells and set up an infection.

Dinglasan hatched the idea as a postdoc in Jacobs-Lorena’s lab. There, he identified a key midgut glycoprotein called aminopeptidase 1 (APN1) that’s present in all mosquitoes. This protein is a digestive enzyme that’s always present in the mosquito midgut, ready to digest a blood meal as soon as the insect consumes one.

However, this protein also appears to play another role: It’s necessary for Plasmodium infection. Dinglasan and his colleagues found that when antibodies to a portion of this protein are present in an infectious blood meal, mosquitoes were 100 percent protected from the parasite.

To get these antibodies efficiently into mosquitoes, Dinglasan relied on the same strategy used by the creators of other transmission-blocking vaccines: creating antibodies in the people that mosquitoes bite. When mosquitoes take a blood meal, they pick up the antibodies.

So far, Dinglasan and his collaborators have produced the protein fragment that serves as an antigen that spurs people to make antibodies to the APN1 protein. In the next two years, they hope to test this vaccine in clinical trials.  To eradicate a disease, Dinglasan says, its cycle of transmission must be broken—that strategy worked for smallpox.

“Malaria researchers have real opportunities to include new approaches to break the cycle of malaria transmission,” Dinglasan says. “We have to take them.”

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