Scientists at QIMR Berghofer Medical Research Institute have developed a protein which completely cures mice of malaria and protects them against re-infection. The breakthrough could lead to a new and more effective way of treating the deadly disease in future.
The findings have been published today in the prestigious journal Immunity.
Malaria is caused by parasites that are spread to humans by the Anopheles mosquito. According to the World Health Organisation (WHO), the disease killed an estimated 438,000 people in 2015. Most deaths are in young children and unborn babies. The WHO estimates that nearly half of the world’s population is at risk of the disease.
Malaria typically causes flu-like symptoms including fever, chills, muscle and joint pain, headache and nausea. It can lead to a lethal brain infection and coma.
The head of the Molecular Immunology laboratory at QIMR Berghofer, Dr Michelle Wykes, and her team discovered that a protein on the surface of a particular immune cell plays a crucial role in fighting malaria infection.
“Within the immune system, there are dendritic cells, which are the generals of the immune army, and there are T cells, which are the soldiers. The dendritic cells tell the T cells when to attack an infection and when to put down their weapons,” Dr Wykes said.
“The dendritic cells have proteins on their surface, which they use to send these orders to the T cells.
“It’s long been known that the job of one of these proteins is to tell the T cells when to switch off and stop fighting. However, contrary to what was previously understood, we found that another protein – called PD-L2 – can override these instructions by telling the T cells to switch on and keep fighting.
“We found that when humans and mice are infected with severe malaria, levels of PD-L2 decrease and so the T cells aren’t being told to keep fighting the parasites.
“We don’t know how malaria manages to block the production of PD-L2. But once we knew how important this protein was for fighting the disease, we developed a synthetic version of it in the laboratory.”
The researchers gave three doses of the protein to mice that had been infected with a lethal dose of malaria.
“All of these mice were cured of the malaria,” Dr Wykes said.
“About five months later, we reinfected the same mice with malaria parasites, but this time we didn’t give them any more of the synthetic protein. All of the mice were completely protected and didn’t become infected.”
Dr Wykes said the findings could form the basis for new ways to treat malaria in future.
“There are drugs available that treat malaria, but emerging drug-resistance is becoming an increasing problem, especially in parts of South-East Asia. Vaccines that are being trialled generally only protect against some species of malaria parasite, and they don’t protect people in the long-term. This means that we urgently need new treatments,” she said.
“Importantly, if this approach is successful, it should treat all species of malaria parasite.
“This would be a completely new way of treating malaria by stimulating a person’s own immune system to destroy the parasites.
“This branch of science – known as immunotherapy – is already showing very positive results for treating some cancers, and we hope that it will be just as successful for treating malaria.”
The research involved collaborators from the University of Queensland’s Institute for Molecular Bioscience and School of Chemistry and Molecular Biosciences; The Queensland University of Technology; Singapore’s Agency for Science, Technology and Research; and, Harvard Medical School in the United States.
It was funded by Australia’s National Health and Medical Research Council and the Australian Research Council.