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Super-antibodies fight off malaria
26 May 2007
From New Scientist Print Edition.
Andy Coghlan

Antibodies taken from Gambian people who are immune to malaria could be used to protect others from infection.

Researchers have long known that certain people are resistant to malaria infection - and that some of them have potent antibodies specific to a protein on the parasite's surface called merozoite surface protein (MSP-1). However, attempts to turn these antibodies into a potential vaccine have been hampered by the lack of suitable animals to test them on. Mice, for example, don't get ill when exposed to Plasmodium falciparum, the blood-borne parasite that causes human malaria - and even if they did, their immune systems wouldn't handle the parasite in the same way as ours does.

Now, Richard Pleass of the University of Nottingham, UK, and his colleagues have created a system for testing the antibodies in mice that solves both these problems. They have used it to extract and refine antibodies taken from 10 Gambian individuals who are immune to malaria, and now hope to test the antibodies in humans.

The researchers started by "humanising" a malaria parasite that normally infects mice, so that when human antibodies were given to mice infected with it, the antibodies would recognise the parasite and bind to it. To do this, they genetically modified Plasmodium berghei (see right), which infects mice, so that instead of making a surface antigen recognised by the mouse immune system, the GM parasite made MSP-1, which the human immune system recognises.

The team then tinkered with the mouse immune system to make it behave more like the human immune system during a malaria infection. They engineered the mice so that their white blood cells would make human Fc-receptor-gamma-1 (FcR1) - the receptor molecule on white blood cells that orchestrates destruction of Plasmodium parasites after they have been captured by antibodies. The system enabled them to test the antibodies they had isolated from the Gambians "for real".

Tests in culture had already shown that the antibodies killed the human malaria parasite, but by giving the GM malaria parasite to mice, Pleass's team proved the antibodies would protect the engineered animals as well. In contrast, mice denied the human antibodies died. The research is published in PLoS Pathogens (DOI: 10.1371/journal.ppat.0030072).

To make the original antibodies from the Gambians more potent, the researchers cloned and reshuffled the genes that make the "jaws" in "Y-shaped" antibodies which grip target antigens. They then screened these newly created "jaws" repeatedly against MSP-1 to identify ones that bound most tightly to it.

From issue 2605 of New Scientist magazine, 26 May 2007, page 16

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