new hope for malaria vaccine

Millions of malaria sufferers have been offered new hope after UK scientists have not only developed a new antibody against malaria but also a way to test it.

Researchers at the University of Nottingham believe their antibody represents a breakthrough  in the search for an effective vaccine. Dr Richard Pleass and colleagues have also genetically engineered mice to be able to test the vaccine candidate - the first time scientists have had an effective animal model for human malaria, they claim.

Malaria infects around 400 million people every year and kills between one and three million, more than any other infectious disease; every 30 seconds, a child dies from malaria. At least   a further 2.3bn people are estimated to be at risk, according to the World Health Organization (WHO). Although treatments are available, there is currently no malaria vaccine.

"Our results are very, very significant," said Dr Pleass, from the Institute of Genetics.

"We have made the best possible animal model you can get in the absence of working on humans or higher primates, as well as developing a novel therapeutic entity."

In the past, drug developers have had no way to test potential vaccines in the absence of humans and higher primates, which has slowed the progress of investigative compounds.

In humans, malaria is most commonly caused by the blood-borne parasite Plasmodium falciparum. Gambian adults immune to malaria produce antibodies that bind strongly to a   region of a parasite antigen called merozoite surface protein 1 (MSP1). The two together then bind   to the Fc-receptor (FcR) found on immune system cells in the human and the parasite   is destroyed.

The team discovered that merely blocking MSP1 was "insufficient to bring about protection"; the presence of FcR is crucial since this allows the parasite to be cleared from the system.  The findings are published in the edition of the open access journal Public Library of Science (PLoS) Pathogens.

However, although the scientists can show that antibodies bind strongly to the malaria  parasite in vitro, these tests don't necessarily predict a good response in humans. Unfortunately, it is also difficult to test anti-malaria antibodies in an animal model, the first  step when moving from in vitro to in vivo test.

For example, mice do not get sick when infected with P. falciparum. To overcome this, Pleass genetically engineered a mouse parasite to produce an antigen that the human immune system recognises.

Then, the researchers altered the mouse's immune system further so that it displayed human FcRs. Now that the animal model had been developed, the team took the antibodies produced naturally by Gambian's immune to malaria and used them to develop their own antibody. In subsequent tests of these antibodies, the mice were cured of "an otherwise lethal malaria infection".

The passive immune response caused by such an antibody, could provide the basis of a new vaccine. Even if this new therapy doesn't ever make it to market, the development of a in vivo test that Pleass described as "has significant advantages over the use of new world primates", could enable others to develop malaria vaccines much quicker.

Source: DrugResearcher
Date: 24 May 2007