The discovery that could turn mosquito bites into vaccine booster shots

After decades of research and a stroke of luck, Australian researchers have developed a new vaccination method for a disease that has dogged humanity for millennia and continues to take at least 610,000 – and counting – lives each year.

The scientists hope the experimental malaria vaccine, successfully tested on mice, could transform mosquito bites into “booster shots” that fortify the body’s immune defences against the disease instead of causing infection.

Malaria is caused by a cunning parasite that has evolved resistance to every major drug designed to treat it. Current vaccines are only 40 to 75 per cent effective, require multiple doses and often suffer from fast-waning immunity.

In response to the crisis, scientists at Melbourne research institute WEHI and their collaborators have fashioned an experimental drug into a kind of chemical vaccine that allows the malaria parasite to grow within the body before killing it right before it causes disease.

That allows the body to build up key antibodies and immune cells ready to pounce on future infection.

“You could think of it as using a drug to convert mosquito bites that spread malaria into vaccination events,” Associate Professor Justin Boddey, corresponding author of the new research published in the major journal Science and a laboratory head at WEHI, said.

Malaria begins when a mosquito bites someone and injects sporozoites, the infectious stage of the parasite, from its salivary glands. The sporozoites wriggle through the blood and into the liver, where they invade cells and rapidly divide.

At this stage, a patient has no symptoms, but after about a week, the parasites burst from infected liver cells as “merozoites” and flood into the bloodstream, infecting and bursting red blood cells.

This marks the symptomatic stage of the infection, when the parasite begins to inflict terrible fevers, headaches, vomiting and possibly death.

Killing the parasite at the late-liver stage – right before it starts sickening a patient – is the “immunogenic sweet spot”, Boddey said.

“What we’ve really happened upon here is the remarkable ability of this drug to permit sporozoite infection and liver stage development all the way through to the late liver stage, and then the drug blocks the parasites from being able to get out and invade red blood cells,” he said.

The huge number of dead parasite cells then prime the body’s lasting immune response. “These large, fat, juicy liver-stage parasites are not causing any disease, but are full of antigens”, which trigger antibodies, Boddey said.

The promise behind the method is that every time someone is bitten, dead parasite cells would build up again, giving the body a chance to re-fortify its immune response. In mice, the treatment generated anti-malarial antibodies and T cells, which learn to recognise the parasite and “execute” infected cells, even after the drug left the body.

Mice given the vaccine and infected with the rodent version of malaria didn’t get sick and, when bitten by 10 malarial mosquitoes almost two years later, retained their immunity.

Using bioengineered mice grafted with human liver cells, the researchers were able to test their treatment on the strain of malaria that infects humans, and showed it also successfully killed the human-adapted version of the parasite.

“Mice have been quite predictive in previous malaria vaccine studies,” Boddey said. “So we’re very excited about the possibility that this will work in people, and we’re ready to start doing clinical trials in this space very, very soon.”

Boddey and two of his colleagues have submitted patents related to the vaccination method.

A major paper in 2017 revealed two malaria proteins called plasmepsin IX and X are essential for malaria to escape liver cells and get into the bloodstream.

Boddey and his colleagues at WEHI and pharmaceutical company MSD had already been working on trying to disrupt a different protein, which didn’t work. But it turned out the drug could disrupt plasmepsin IX and X.

That’s the discovery that allowed the scientists to turn liver cells from a parasite nursery into a death trap.

“It’s a bit of a dream come true, and it’s a huge team effort,” Boddey said. “Chance favours the prepared.”

Malaria researcher Dr Claire Sayers, a molecular biologist at the University of NSW who wasn’t involved in the study, said the new research addressed the major challenge of both stopping malaria and building long-term immunity.

“This is an exciting preclinical study that presents an innovative approach to tackling malaria and showcases the value of discovery science,” she said.

“The critical next step will be to see whether this promising approach can translate into meaningful protection in people under real-world conditions of malaria exposure.”

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