Novel approach to malaria vaccine
Researchers have identified the main toxin contributing to the virulence of malaria in mice, and maybe humans, raising hopes that a new vaccine to treat the disease is not far off.
Reporting in this week's issue of Nature, Dr Louis Schofield at Melbourne's Walter and Eliza Hall Institute of Medical Research and colleagues from the Massachusetts Institute of Technology present a strong case for developing a vaccine against the toxin, called glycosylphosphatidylinositol (GPI).
Unlike other approaches to developing a malaria vaccine, which aim to kill the parasite, an anti-GPI vaccine would work by blocking the toxin.
Malaria kills two million people every year, and 5 to 10 per cent of the world's population infected by Plasmodium falciparum, the single-celled parasite species responsible for the most serious cases of the disease.
The new discovery comes more than 100 years after renowned scientist Camillo Golgi first proposed in 1886 that malaria parasites produce a toxin associated with the intense periodic fevers caused by infection.
His hypothesis gained more weight in 1993, when Dr Schofield and his team showed that GPI had the properties of a toxin, producing a potent inflammatory response in cell culture and mice.
GPI is a glycolipid, a molecule consisting of sugar and fat that is a component of cell membranes found in most complex organisms, albeit in subtly different forms.
In their latest studies, the researchers found that a glycan chain, the core component of GPI in malaria parasites, makes it function as a toxin.
"That's why we reasoned this glycan would be a good candidate for use as a vaccine," explained Dr Schofield.
The researchers synthesised a non-toxic form of the GPI glycan, then coupled the synthetic glycan to large carrier molecules in order to trigger recognition by the immune system.
In initial tests, they found that the anti-GPI vaccine provoked an antibody response in mice.
Not only that, when the vaccinated mice were injected with malaria parasites and malaria developed in their blood, they did not get sick and die.
The standard anti-malarial drugs are chloroquine and mefloquine. But malaria parasites are rapidly becoming resistant to these, creating a big demand for new drugs.
Vaccines as an alternative to drug therapy for malaria have been hoped for ever since it was first observed in 1900 that people could develop immunity to malaria.
Dr Schofield emphasises that since GPI is an essential molecule in all malaria parasites, a successful anti-GPI vaccine for use in humans could prove permanently effective.