Despite the advances in science, we haven’t been able to create a vaccine against malaria – a mosquito-borne illness that kills as many as quarter of a million people annually. This is about to change as scientists at Johns Hopkins Bloomberg School of Public Health have identified a potential and promising new target that can be used to develop a vaccine against the disease.
According to latest statistics, half the world’s population is at risk for malaria and the vast majority of those who succumb to the parasite – as many as 90 per cent – are children under age five, most of them in sub-Saharan Africa.
For the latest research, scientists created a 3-D crystal structure of the protein which is believed to be central to the transmission of the malaria parasite through mosquitoes. Dubbed AnAPN1, the protein is found in the gut of the Anopheles mosquito and upon closer look they found that previous vaccine candidates targeted irrelevant regions of the protein and that’s the reason the vaccines were not able to offer the protection despite of their promising results when tested on mice.
The researchers had originally looked at fragments of the AnAPN1 protein in order to understand its role in parasite transmission. Study’s leader Rhoel R. Dinglasan, PhD, MPH, an assistant professor in the Bloomberg School’s Department of Molecular Microbiology and Immunology and also a member of the Johns Hopkins Malaria Research Institute equates this process as that of examining a tree by cutting it into planks.
Dinglasan said that this strategy doesn’t really give a whole picture of the tree and chances are that some key things may be missed out.
Dinglasan and colleagues decided to look at the whole protein and not its fragments. “Here we have for the first time a chance to look at the whole tree and have discovered a part we never appreciated before. The missing link had been understanding what was the most important part of the protein to target to prevent transmission of the malaria parasite. Now we believe we have found our new target”, the researcher said.
The goal of the new research is to stop the transmission of Malaria in its tracks. To do this, Dinglasan’s new vaccine destroys the Plasmodium parasite’s ability to move on to infect the next person. Dinglasan explains that a mosquito becomes infected by the parasite when the parasite is able to invade the mosquito’s gut before it can be digested. This is what they are targeting – obscuring the newly discovered portion of AnAPN1 – to prvent the parasite from essentially grasping the handle to open the door to the gut.
Dinglasan and his team, including Natalie A. Borg, of Monash University in Melbourne, Australia, mined the crystal structure of AnAPN1 to generate a map of each part of the protein.
Using the crystal structure, researchers were able to identify the binding site of a particularly potent antibody to malaria as the new region of AnAPN1. They tested these antibodies using blood samples taken from children carrying the malaria parasite in the nation of Cameroon, one of the countries greatly impacted by malaria. They found that very small amounts of the antibody completely prevented transmission of the parasite to the mosquito across all of their samples.
While this brings the team one step closer to a clinical trial, Dinglasan cautions that there is more work to be done. He also thinks a vaccine based on this concept could complement a current vaccine being tested that is somewhat effective in lessening the effects of malaria in people. People who survive malaria or have low-grade malaria are carriers of the disease. When those people are bitten by uninfected mosquitoes, the mosquitoes can then become infected, perpetuating the disease in a community. If scientists can “vaccinate” mosquitoes, it could go a long way toward eradicating the disease, he says.
“We are focused on the mosquito as a way to stamp out malaria,” he says. “For more than 100 years, we have studied the parasite as the key to stamping out malaria but we haven’t gotten very far. The parasite has to go through the mosquito to continue its life cycle before being able to infect humans. Our approach could stop the disease by halting the infection of the mosquito.”
These new findings suggest researchers were probably asking the immune system to target too many regions on AnAPN1, which only diluted the response to the relevant regions of the protein. Dinglasan has now redesigned his vaccine to focus on this newly understood region of AnAPN1.
The findings have been published in the journal Nature Structural & Molecular Biology.
