New malaria center for Johns Hopkins

URBANA, ILLINOIS Malaria kills more than two million people per year and causes sickness in 300–500 million. But despite the continuing toll, funding for malaria research, treatment and prevention has been scarce and two decades of efforts to develop a vaccine have so far been unsuccessful. The situation grew so dire that the Institute of Medicine concluded in a 1996 report that "the outlook for malaria control is grim."So it was big news when an anonymous donor gave a $100 million on 7 May to the Bloomberg School of Public Health at Johns Hopkins University in Baltimore for a new research center devoted entirely to understanding and stopping malaria.That funding is the latest of several initiatives to combat the disease, including a new research push from the National Institutes of Health — also announced 7 May — to boost malaria, tuberculosis and HIV research, $115 million from the Bill and Melinda Gates Foundation for three different initiatives to develop malaria drugs, vaccines and infrastructure for new clinical trials, and a $100 million effort by the World Health Organization intended to half the disease burden by 2010.Still, it's not clear whether the new efforts will be enough, and when, if ever, research will yield effective measures to control malaria. "The problem is that the parasites that cause the infections are becoming globally resistant to antimalarial drugs and any new drugs that are being developed are too expensive," says Nirbhay Kumar, a malaria researcher and professor at the Bloomberg School of Public Health. Although chloroquine and other antiparasite drugs, and bed nets soaked with pyrethroid insecticides provide some protection — studies are ongoing to see how much — the measures are a stopgap until a vaccine can be developed, Kumar says. "Vaccines against the disease would provide cost-effective and long-lasting protection," he says.Such vaccines would have a global impact, according to the authors of the Institute of Medicine report, who wrote that an effective malaria vaccine "could be one of the most important advances in medicine, with the potential for improving the lives of hundreds of millions of people."Effective vaccines are indeed the ultimate goal of the new research, says Alfred Sommer, Dean of the Bloomberg School. But to get there, researchers still have a lot to learn about malaria. Johns Hopkins plans to spend the $100 million over 7–10 years to build the new Johns Hopkins Malaria Institute and pay for about 12 top researchers, to be hired over five years. The university won't say who it hopes to attract — no one's signed up yet and the negotiations are ongoing — but the researchers will come from a variety of disciplines, including entomology, parasitology, immunology and vaccine development, says Sommer. The idea, he says, is to bring bright young researchers from cutting edge fields to create "a rich creative brew." The money will allow them to pursue innovative but risky research that would never make it through an NIH study section, which are typically risk-averse.Sounds great, but is malaria research really ready for prime time? "We have to be realistic, says Altaf Lal, chief of the molecular vaccine section at the Centers for Disease Control. Even after two decades of research and numerous vaccine trials, "we don't have a vaccine at this time."The complexity of the disease makes developing vaccines a challenge, Kumar says. For starters, four related but different species of Plasmodium parasite cause malaria. Two of them, P. falciparum and P. vivax, each account for a similar number of cases and together they account for more than 95% of all cases. All current vaccine efforts aim to protect against P. falciparum because it causes the vast majority of malaria deaths.To complicate matters, public health officials want two types of vaccine. One would protect people who live in countries where malaria is endemic from repeat infections. The other would protect travellers such as tourists and military personnel.In addition, vaccines could be targeted at different stages of the Plasmodium life cycle: the sporozoite that is passed from an infected Anopheles mosquito into the blood stream and migrates to the liver; the merozoite that invades red blood cells, causing the symptoms of malaria; or the gametocyte, the sexual form that can combine in the mosquito and mature to form the sporozoite.The vaccines that have been tested in humans aim to block the sporozoite from invading the liver. The most advanced vaccine candidate, which is being evaluated for safety in a phase I clinical trial in children in The Gambia, showed 70% efficacy in adults but only for a short period, says Regina Rabinovich, director of the Maryland-based Malaria Vaccine Initiative, which is funded by the Bill and Melinda Gates Foundation. The vaccine was developed by the Walter Reid Army Medical Center in Washington DC, and is being manufactured by GlaxoSmithKline. A small trial to test for efficacy is slated for 2002, she adds.Prototype vaccines of this type have failed for several reasons, Rabinovich says. Many don't provoke enough of an immune response, so there's a need for better adjuvants. Nor is there yet a satisfactory method of delivery, or platform, Rabinovich says. "If we can get a vaccine to work well, we can improve it. But we haven't solved what platform will really work."There are promising strategies in the pipeline that target the other stages of the Plasmodium life cycle. Some block the merozoite, and Kumar and others are even working on a human vaccine that stimulates and antibody response to block the parasite from reproducing sexually in the mosquito. Vaccines aimed at different life stages might have to be combined to get the best results, Kumar says.Despite the challenge, Johns Hopkins officials are optimistic. The genomes of P. falciparum, P. vivax and the Anopheles mosquito will soon have been sequenced, which will allow the identification of the molecules involved in the interaction between mosquito, parasite and human. In addition, improved population genetics may allow the prediction of outbreaks, which is currently impossible, so that vaccine can be targeted to outbreak areas.By the time the money runs out sometime between 2008 and 2011, Sommer says they hope to have developed new vaccines for clinical testing. And if they're not ready by then? "The donor has indicated that if they still have the means and if we make significant progress, they'd be interested in making another gift," he says.

New malaria center for Johns Hopkins

Malaria research has been underfunded for decades. Now, a $100 million donation to Johns Hopkins University should allow much-needed progress on vaccines.

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