PhD student Vashti Irani, Burnet Institute Centre for Biomedical Research - Beeson/Richards Lab

Burnet Institute scientists have identified an important mechanism by which human antibodies are able to stop malaria from invading red blood cells and causing disease – a potentially significant step in the quest for effective malaria vaccines.

The research team, led by Professor James Beeson and Dr Jack Richards, focused on a protein, EBA-175 which malaria uses to bind to a receptor on the human red blood cell prior to invading the cell.

The research paper is published in Clinical Infectious Diseases, where it attracted an editorial commentary by Professor Chandy John, the Ryan White Professor of Pediatrics at University of Iowa.

PhD student Vashti Irani, who performed key studies in the project, said it was well known that people who live in malaria-prone areas commonly produce antibodies to EBA–175, but there was little understanding of how these antibodies block malaria, or how important these are.

“So we developed different methods to measure the function of the antibodies and we were able to show that the antibodies bind to the protein, EBA-175, and stop it from interacting with the red blood cell receptor,” Ms Irani said.

“Importantly, these blocking antibodies were associated with protection against malaria in children, suggesting this is an important mechanism in immunity.”

The Burnet team studied a cohort of children from Madang in Papua New Guinea aged five to 14 years who were developing immunity to malaria, in collaboration with colleagues at the PNG Institute of Medical Research.

The data showed a strong association between binding inhibitory antibodies to EBA-175 and a high level of protection from clinical malaria.

“Knowing how these antibodies function is important, because if we ever want to develop a vaccine we need to understand what kind of immune response we would want to generate,” Ms Irani said.

“That’s the next part of my PhD, to determine how well our existing vaccines can induce this type of immunity, and develop vaccine approaches to maximise this.

“I think it’s very exciting because we still have to ask a lot of basic questions about how antibodies act, and this research brings us a step closer to knowing what’s happening in naturally-acquired immunity and the best ways to target malaria through vaccines.”