Image: Ibrahim Boran

Scientists have taken another big step forward towards developing a vaccine that’s effective against the most severe forms of malaria.

Professor Denise Doolan from James Cook University’s Australian Institute of Tropical Health and Medicine (AITHM) was part of an international team that narrowed down the malaria proteins and disease-fighting antibodies that could be used to develop a vaccine against severe malaria.

She said according to the latest figures from the World Health Organisation, there were 219 million cases of malaria worldwide in 2017, leading to an estimated 435,000 deaths.

“What makes this work so difficult is the particular survival strategy of the malaria parasite in the human body. It grows within blood cells and inserts proteins into the surface of the blood cell so it sticks to the walls of blood vessels,” Professor Doolan said.

“But it changes these proteins to escape from immune responses, and every strain has a different set of proteins, making the identification of vaccine targets extraordinarily hard.”

The team of collaborators – involving JCU, the Walter and Eliza Hall Institute of Medical Research (WEHI) at Deakin University, and malaria experts from Papua New Guinea, France and the USA – collected hundreds of PfEMP1 proteins from malaria strains from children in PNG who had been naturally infected by the disease, made a custom protein microarray of those strains, and then examined serum samples to identify which of the many PfEMP1 variants were associated with protection.

The research team managed to pinpoint which antibodies were most effective in fighting the most severe forms of malaria.

Associate Professor Alyssa Barry, who leads the Systems Epidemiology of Infection unit within the Deakin School of Medicine, said the findings from the project were a major step towards developing a viable vaccine for the disease.

“It’s the first time anyone has shown this – for years, researchers have thought that developing a malaria vaccine based on PfEMP1 would be virtually impossible, because the proteins are just so diverse,” Associate Professor Barry said.

“It’s similar to the flu vaccine, where you have to keep adjusting and updating it as the virus strains evolve from year to year. Malaria is even more diverse than influenza – one village in a country such as PNG could contain thousands of possible malaria strains. But in malaria-endemic areas, children who are repeatedly infected develop immunity to severe malaria by the time they’re about two years old, so we know antimalarial immunity is possible, and it can develop after exposure to only a few strains.”

Associate Professor Barry said while immunity to milder forms of malaria presented a “formidable obstacle”, immunity to severe malaria targets only a small subset of proteins that have many similarities between strains – making the essential components for a vaccine much easier to identify.

“Using genomic sequencing, we collected PfEMP1 proteins from different strains of malaria, measured antibodies to those proteins and then used machine learning to identify the protective antibody – the biomarker of immunity – that protects kids against disease,” she said.

“We were able to identify these antibodies by monitoring for patterns of disease, following the children in PNG for 16 months to determine which of them were susceptible to the more severe forms of the disease, and those who were protected and only experienced milder forms of the disease.

“It’s been a long road, and has involved a large team, but it’s a major step forward, and this provides hope that creating a vaccine might be possible.”

The full research findings, “Protective immunity against severe malaria in children is associated with a limited repertoire of antibodies to conserved PfEMP1 variants”, were published today in the scientific journal Cell Host & Microbe.