Protected by Crippled Parasites

8 December 2004 (All day)

Tough customer. Researchers say a form of P.falciparum weakened by genetic engineering could be the secret to an effective malaria vaccine.

A new malaria vaccine, produced by weakening the parasites that cause the disease, has been successfully tested in mice. The study offers a new strategy to tackle one of the most urgent and difficult challenges faced by vaccine makers.

Malaria kills more than a million people a year, most of them African children. Drugs and bed nets can reduce that number, but a vaccine is widely believed to be the best bet. But no vaccine against any parasitic disease exists at the moment, and researchers believe parasites' complex lifecycles and large genomes make them much more elusive targets than viruses and bacteria. A recent study showed that one leading malaria vaccine candidate had only limited efficacy in people (ScienceNOW, 14 October).

One promising approach is to make vaccines from live parasites that have been weakened by radiation so they can no longer reproduce and cause disease. Studies with Plasmodium falciparum--the parasite causing the most serious form of human malaria--have shown that inoculation with such crippled parasites can indeed protect most people from real malaria. Sanaria, a company in Rockville, Maryland, is developing a vaccine based on the concept.

Now, Ann-Kristin Mueller at the University of Heidelberg, Germany--along with colleagues at University of Washington in Seattle and the Seattle Biomedical Research Institute--have found a subtler and more precise way to deal parasites a debilitating punch. In a study published online 5 December in Nature, the team shows that by knocking out a crucial gene, called UIS3, they can render Plasmodium berghei, which infect rodents, unable to invade the liver, which is the first stage in malaria. When mice were inoculated with these weakened parasites in a so-called prime-boost regimen, they were completely protected when they were later challenged with P. berghei.

The team still needs to delete the corresponding gene in P. falciparum, and just to be on the safe side, it may be better to knock out one or two more, says Sanaria chief Stephen Hoffman. Still, the study offers an exciting new way to weaken parasites, he says. Hoffman says he's talking to the team about collaboration with Sanaria, which has experience with large-scale production of weakened parasites under conditions that satisfy regulatory authorities.

Related sites
A review of malaria vaccines currently in development
More about malaria from the World Health Organization

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