The sequence of a malaria merezoite binding to a red blood cell just before it infects the cell.

Researchers at Burnet Institute have gained important new insights into how malaria infects human cells that will advance the quest for new drugs and vaccines against the disease.

Malaria remains as one of the world’s biggest killers, particularly among young children. It is caused by a pathogen called Plasmodium, which infects human red blood cells and replicates inside them. Understanding how malaria infects red blood cells, and how to effectively block that process, is essential in order to develop new treatments and vaccines for malaria.

It is the merozoite form of malaria pathogen that sticks to red blood cells and then burrows into the cell and infects it. To achieve this, malaria merozoites produce a variety of proteins and many of these proteins are being investigated as possible vaccine targets. However, the precise functions and roles of proteins on the merozoite surface are largely unknown.

New research led by Dr Michelle Boyle and Professor James Beeson shows that the merozoite is armed with a multitude of proteins on its surface that play different roles in infection of red blood cells, and that layers of specific proteins are sequentially cleaved or ‘peeled-off’ during the different steps of infection.

“Some proteins are required for binding to red blood cells, whereas others are used by malaria for initial development once inside the red blood cell,” Professor Beeson, Head of Burnet’s Centre for Biomedical Research explained.

“We also showed that some antibodies generated by vaccines that are designed to block this process are ineffective.”

Although the antibodies can stick to malaria merozoites, the pathogen is able to resist attack and successfully infect red blood cells.

“So, targeting the right proteins and avoiding malaria’s defences – finding the weakness in malaria’s coat - is a strategy for vaccine development and opens new avenues for developing antimalarial drugs,” Professor Beeson said.

The study was published in the international journal Infection and Immunity, with an accompanying commentary by Boston Children’s Hospital Assistant Professor of Pediatrics, Dr Jeffrey Dvorin.

In the commentary Dr Dvorin noted that ‘this provides a new fundamental biological step in the parasite life cycle that can be investigated and hopefully targeted and/or blocked by new vaccines or antimalarial therapeutics.’

The research involved collaboration between researchers at Burnet Institute, Walter and Eliza Hall Institute, Monash University, and LaTrobe University. Funding was provided by NHMRC, ARC, and Victorian State Government operational infrastructure support grant.

Links to papers
http://iai.asm.org/content/82/3/924.long
http://iai.asm.org/content/82/3/921.long