BioWorld International Correspondent

LONDON - An experimental vaccine against malaria has been able to reduce the risk of a severe attack of the disease by more than three-quarters in children between 1 and 2 years old - a group that suffers acutely from the severe and often fatal form of malaria.

An efficacy trial completed in May showed that the vaccine was safe, immunogenic and partially effective in preventing malaria. The placebo-controlled study, carried out in more than 2,000 children ages 1 to 4, found that children who received the vaccine were 30 percent less likely to suffer clinical malaria during the study than those who received placebo. The risk of severe and complicated malaria was 58 percent lower in the vaccine group.

Pedro Alonso, head of the Centre for International Health at the University Hospital of Barcelona in Spain and scientific director of the Manhiça Health Research Centre in Manhiça, Maputo Province, Mozambique, where the study was carried out, told BioWorld International: "For many years, there has been a heated debate among the international community as to whether a malaria vaccine is possible or not, but our results show conclusively that, yes, a malaria vaccine is possible."

He attributed the success to the use of new adjuvants that help stimulate the required immune response, and he predicted that a similar approach with other candidate vaccines against other diseases might improve their efficacy.

Alonso and his colleagues carried out the study with collaborators in Barcelona and Mozambique, and in conjunction with GlaxoSmithKline Pharmaceuticals, of Rixensart, Belgium, and the Malaria Vaccine Initiative in Rockville, Md. The team hopes to complete testing and registration of the vaccine by 2010. Their long-term aim is to prove the vaccine in infants under the age of 1 year, with the expectation that it would be possible to include the vaccine in the expanded program of immunization.

The trial is reported in the Oct. 16, 2004, issue of The Lancet in a paper titled "Efficacy of the RTS,S/AS02A vaccine against Plasmodium falciparum infection and disease in young African children: randomised controlled trial."

Half of the world's population lives in areas where malaria is endemic. There are between 300 million and 500 million cases of malaria each year, and the disease claims an estimated 1 million to 3 million lives each year, most of them children in sub-Saharan Africa. The most severe form of malaria is caused by the parasite Plasmodium falciparum.

Progress toward a vaccine to protect against malaria has been particularly slow, Alonso said, because scientists had failed to identify immunological markers that correlated with protection against the disease. As a result, human clinical trials have been the only way to evaluate whether a candidate vaccine works.

The complex life cycle of the parasite also has presented difficulties. P. falciparum is injected along with the saliva of the infected mosquito when it bites a human. The parasites, in the form of sporozoites, enter the bloodstream and then, after a few minutes, invade liver cells. There, they grow and multiply, eventually releasing merozoites into the blood, which cause the distinctive symptoms of malaria, such as high temperature, headache and diarrhea.

The vaccine used for the trial reported in The Lancet aims to stimulate an immune response against the sporozoite form of the parasite. It contains two polypeptides, called RTS and S, from the circumsporozoite protein of P. falciparum. For the vaccine, the genes encoding those polypeptides are expressed in yeast and then fused to the hepatitis B surface antigen.

That complex is manipulated to form particles and combined with an adjuvant called AS02A, which is an oil-in-water emulsion of two immunostimulants: monophosphoryl lipid A and Quillaja saponaria fraction 21.

Early trials of the vaccine in U.S. military volunteers and in partially immune adults in the Gambia, West Africa, had been encouraging. However, Alonso said, "this trial provides the first evidence that this vaccine not only reduces new infections, but that it also reduces the risk of clinical malaria and reduces the number of episodes of severe malaria." The vaccine stimulated production of antibodies and cell-mediated immunity of the Th1 type.

The vaccine will not be recommended for use by travelers to endemic regions, Alonso said, because it is less effective than the preventive drugs that are used at the moment.