Protein microarray uncovers malaria immunity

Not everyone responds to malaria in the same way. In fact, some people can eventually develop an immunity to the parasite, showing only mild symptoms, or even none at all, if they’re infected.

Dr Alyssa Barry from the Walter and Eliza Hall Institute’s Infection and Immunity division employed a new technique to explore the ins and outs of this malaria immunity by tracking which variations of malaria proteins an individual is immune to.

A deeper understanding of malaria immunity, and the proteins that trigger an immune response, could lead to improved malaria diagnostics and may highlight some drug targets for a malaria vaccine.

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Barry used protein microarrays to track a particular protein found in malaria. “We know that one protein, called PfEMP1, that is particularly important for the host immune response can be produced in many different varieties, and these can be altered by the parasite to avoid detection by the immune system,” she said.

Barry and colleagues at the Queensland Institute of Medical Research, the Papua New Guinea Institute of Medical Research and the University of California Irvine, adapted existing protein microarray technology to allow small samples of human serum (less than one hundredth of a millilitre) to be tested simultaneously against hundreds of variants of PfEMP1 to determine to which variants the person was immune.

The team found that children under two in one region of Papua New Guinea, where malaria is endemic, are immune to only a few specific variants of PfEMP1, while older children and adults show immunity to an increasing range of PfEMP1 variants.

“Young children are the most vulnerable to malaria,” she said. “Our studies show that this is partly because they have not developed immunity to the many different malaria variants to which they are exposed.

“As people get older, they become immune to a wider spectrum of malaria parasites, and so when they are infected they develop milder disease and eventually do not develop disease at all, although they can still be infected.”

The team is now undertaking a larger study that will screen more people from other regions of Papua New Guinea, and will screen a wider variety of Plasmodium protein variants.

Barry hopes the research will lead to the development of a diagnostic test for susceptibility to malaria and also determine which proteins might be the best to use as the basis for a malaria vaccine.

“We currently do not know how people become immune to malaria,” she said. “Our protein microarray technology could assist in monitoring malaria control and elimination programs, by showing when a population becomes more susceptible to the disease as a result of waning immunity.”

The research was published in Molecular and Cellular Proteomics.