Scientists at La Trobe University have identified a novel antibody-like molecule, WD34, with the potential to prevent infection from multiple malaria parasite species. The research, published in Nature Communications, reveals that WD34 inhibits the ability of malaria parasites to infect cells at different stages of the disease by binding to the AMA1 protein. This breakthrough could lead to the development of a broad-spectrum malaria therapy, addressing the urgent need for new treatments in the face of increasing drug resistance.
Targeting AMA1 for Broad-Spectrum Protection
The study, led by Professor Michael Foley, Professor Robin Anders, and Ph.D. candidate Dimuthu Angage at the La Trobe Institute for Molecular Science (LIMS), demonstrated that WD34 binds to the AMA1 protein, which is crucial for malaria parasite entry into both liver and red blood cells. Malaria parasites inject into the bloodstream via infected mosquitoes, travel to the liver, and later re-enter the bloodstream to infect red blood cells. To enter these cells, parasites use AMA1 and another protein called RON2, which bind together to open cell walls. WD34 effectively blocks this mechanism by binding to AMA1 at the same site as RON2.
Professor Foley emphasized the significance of this discovery, stating, "We urgently need broader therapeutic options to combat drug resistance and treatment failures, and this discovery provides some hope for the development of a treatment for all malaria parasite species." He noted that malaria remains a deadly parasitic disease, infecting over 240 million people annually and causing more than half a million deaths worldwide.
Overcoming AMA1 Polymorphism
One of the key challenges in developing a broad-spectrum malaria vaccine has been the polymorphic nature of AMA1, meaning that each strain has a different form. However, the researchers found that the region where AMA1 binds with RON2 is conserved across different strains. "The AMA1 variations between parasite species have in the past hindered efforts to find a broad-spectrum vaccine. That's why identifying WD34 is such an important breakthrough, as it targets this conserved region and can bind with the various versions of AMA1 produced by different malaria parasite species," Professor Foley explained.
Pre-clinical Trials and Future Directions
WD34 is currently undergoing pre-clinical trials and has shown promising results as a potential shield against malaria. The antibody screening method developed by Angage is also being explored for its potential in researching other infectious diseases. This research was a collaborative effort involving scientists at the Walter and Eliza Hall Institute, the Burnet Institute, and the University of Adelaide.
With the rise of drug-resistant parasites and insecticide-resistant mosquitoes, the development of WD34 offers a new avenue for creating a vaccine that targets all malaria species. "WD34 offers hope by opening new avenues of research to develop a vaccine which targets all malaria species," Professor Foley concluded.
