Source: Steve Bryson, PhD

Malaria is one of the most inflicting infectious diseases worldwide. Each year, an estimated 200 million people contract malaria and approximately 440,000 people succumb to the infectious disease.

Scientists in the Julien lab at The Hospital for Sick Children (SickKids) and their collaborators at the German Cancer Research Center (DKFZ) in Heidelberg, Germany, have studied how the human immune system combats malaria infections. In this study, the researchers discovered a previously unnoticed characteristic of antibodies against the malaria parasite: They can cooperate with each other, thus binding even stronger to the pathogen and improving the immune response. The results, now published in Science, are expected to help develop a more effective vaccine against the disease.

The antibodies described in this study were obtained from participants who had repeated contacts with the parasite and became protected against malaria in a vaccine trial conducted by Sanaria and the University of Tubingen. For an antibody to prevent infection effectively, its affinity (the strength of its interaction with the pathogen) is pivotal. The immune system specifically multiplies antibodies with high affinity to ensure they are present if the body gets infected with the same pathogen again. Among the antibodies studied, the SickKids and DKFZ scientists found a group that displayed a previously unnoticed characteristic that appears to be valuable for the immune system: They interact directly with each other. X-ray crystallography, single-particle electron microscopy and biophysical experiments performed by CIHR postdoctoral fellow Stephen Scally and Alexandre Bosch in the Julien lab revealed that neighboring antibodies can interact directly among each other because they target a repeating protein motif on the malaria pathogen’s surface.

Next, the scientists plan to investigate how their results may be used to improve immunization protection against malaria and bring them one step closer to a malaria vaccine. In addition, they will explore whether these observations can be transferred to other repetitive molecules that are present on other pathogens. This work was undertaken, in part, thanks to funding from the Bill and Melinda Gates Foundation, the Canada Research Chairs Program, the SickKids Foundation, the Canadian Institutes of Health Research and the German Research Foundation (DFG).