Developing a Vaccine Against Severe Malaria

Developing a malaria vaccine based on the PfEMP1 proteins has been thought to be impossible since these proteins are so diverse. But in a study published today in Cell Host & Microbe, researchers found a way to narrow down which anti-PfEMP1 antibodies were most effective against severe malaria.

Malaria parasites grow within red blood cells, where they insert PfEMP1 proteins into the surface. “As part of their survival strategy within the human host, malaria parasites use PfEMP1 to stick to the walls of blood vessels, and this can cause blockages to blood flow and inflammation, leading to severe disease,” says senior author Alyssa Barry of Deakin University. “Malaria parasites change these proteins to escape from developing immune responses, and every strain has a different set of proteins, making the identification of vaccine targets like finding a needle in a haystack.”

The team managed to pinpoint which antibodies were most effective in fighting the most severe forms of malaria by using antibody measurements from hundreds of different variants of the PfEMP1 proteins. The team collected hundreds of PfEMP1 proteins from malaria strains from children in PNG who had been naturally infected by the disease.

“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 PfEMP1 variants,” Barry says. “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.”

According to Barry, 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 to identify the protective antibody—the biomarker of immunity—that protects kids against disease,” she says. “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.”