Synthetic protein offers hope of malaria cure

A protein called PD-L2 could help stimulate a person's own immune system to fight malaria(Credit: J J Harrison/CC SA 3.0)

Of the serious diseases transmitted by the mosquito, malaria is one of the most common and dangerous, killing hundreds of thousands of people each year. Now, scientists have developed a synthetic protein which not only completely cures malaria in mice, but also prevents the disease from recurring down the track.

According to the World Health Organization (WHO), malaria was responsible for an estimated 438,000 deaths last year. Initially, symptoms seem flu-like, including nausea, fever, headaches and sore joints and muscles, but things get worse if left untreated, and could eventually end in death.

"There are drugs available that treat malaria, but emerging drug-resistance is becoming an increasing problem, especially in parts of South-East Asia," said Dr. Michelle Wykes, head of the Molecular Immunology laboratory at QIMR Berghofer Medical Research Institute in Australia. "Vaccines that are being trialed 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."

Research conducted at the Institute may have uncovered a new solution. A certain protein helps the immune system fight off infection, but advanced malaria tends to suppress that protein. Realizing this, the team synthesized their own version of it.

"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," Wykes explained. "The dendritic cells tell the T cells when to attack an infection and when to put down their weapons."

For that job, the dendritic cells use proteins on their surface, including one that instructs the T cells to switch off. But another, called PD-L2, is able to override those instructions, ordering the T cells to keep fighting the good fight.

"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," said Wykes. "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."

To test it out, the researchers infected mice with a lethal dose of malaria, before administering three doses of their synthetic protein. All of them were cured. In addition, when the same mice were reinfected with the parasites five months later, the infection couldn't take hold so a further dose of the synthetic protein wasn't necessary.

"This would be a completely new way of treating malaria by stimulating a person's own immune system to destroy the parasites," Wykes said.

The research was published in the journal Immunity.

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