Quest for malaria vaccine revs up, but much work remains.

Abstract

Quest for malaria vaccine revs up, but much work remains: after upwards of 75 human trials -- mostly small-scale, but a few full-scale, field trials -- and with dozens more being planned, malaria vaccines are coming of age. Money has begun to pour into vaccine trials from both public and private sources, and new ideas and approaches are proliferating. Researchers are upbeat, but how long will it be before a good malaria vaccine becomes available. (News Features) With the influx of new money -- probably ten times as much as was available over the last decade -- malaria vaccine research and vaccine development are booming. And with the new knowledge of the human genome, and the almost complete sequencing of the malaria genome, hundreds of new components of the malaria parasite are being discovered that might stimulate the immune system, to add to the mere dozen or so that have been worked on by vaccine researchers to date. So far, the most promising results, in the view of the majority, of experts interviewed for this article, have been seen with a vaccine that has emerged from a 17-year collaborative effort involving several teams. The vaccine, code-named "RTS,S", is a combination of molecules from the malaria parasite and others from the hepatitis B virus, combined into a single particle that incorporates a specially designed immune-stimulating, or adjuvant, substance. It was developed by the drug firm GlaxoSmithKline (and its predecessors), in partnership with, among others, the Walter Reed Army Institute of Research. In a preliminary trial, the vaccine protected 70% of adult volunteers in the Gambia against infection with Plasmodium falciparum, the most lethal of the four malaria parasites that infect humans, but the protective effect waned rapidly after two months. Dr Joe Cohen, head of vaccines for emerging diseases at GlaxoSmithKline told the Bulletin that the vaccine is "targeted to infants and children living in malaria-endemic regions". An early-stage (Phase 1) trial is currently under way in children in the Gambia, primarily to test the vaccine for safety. "If all goes well, an efficacy, or Phase 2b, trial will take place in an African country in 2002 to tell us to what extent the vaccine reduces malaria disease." Much larger (Phase 3) trials would then be started "to evaluate the impact of the vaccine on morbidity and mortality in children and infants." The initial series of Phase 1/2b trials, which will cost nearly US$ 7 million, is being conducted in partnership with the US$ 50 million Malaria Vaccine Initiative (MVI) lauched 18 months ago by Microsoft entrepreneur Bill Gates and based at the Seattle headquarters of the Program for Appropriate Technology in Health (PATH). The second most promising vaccine candidate, according to many experts, is an Australian "combination B", vaccine, that combines immune-stimulating molecular structures (antigens) from the asexual blood stages of the malaria parasite's life cycle (see Box). It has been tested in children in Papua New Guinea by a team from the Papua New Guinea Institute of Medical Research and their collaborators at the Swiss Tropical Institute in Basel, Switzerland. In this trial, still to be published, the vaccine induced a substantial reduction in parasite densities in the bloodstream over a period of at least four months, and could, say the researchers, be potentially life-saving, especially in children. The duration of protection, however, has not yet been studied. To create a useful vaccine against such a complex organism as the malaria parasite, with its different life cycle stages, each involving a distinct set of immunologically operational antigens (see Box), is far from easy. Dr Tom Richie, head of clinical trials at the Naval Medical Research Center's malaria program in Silver Spring, Maryland, which hosts one of the world's largest malaria vaccine research programmes, points out that malaria is a chronic infection, whereas successful human vaccines so far "are almost all against acute infections or the acute stage of an infection. …