Mosquito Production Mooted As Fast Track to Malaria Vaccine
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news Route to success Opening doors Getting together Demolition job Roadmap lays out Harvard’s systems Moves are afoot on a Indian minister quits future for US biology head sees transnational research over destruction of biomedical research vision become reality agency for Europe mosque p438 p439 p440 p442 Mosquito production mooted as fast track to malaria vaccine Declan Butler,Paris A leading US researcher is probing an auda- cious approach to develop a malaria vaccine by cultivating billions of parasites, irradiated to stop them causing disease,in swarms of live mosquitoes. The approach, which builds on experi- mental results that are 35 years old, is viewed by other top malaria researchers with a mix- A. D. HOFFMAN & R. C. THOMPSON ture of curiosity,incredulity and admiration. But its proponent, Stephen Hoffman, founder of Sanaria, a company based in Gaithersburg, Maryland, says he has become disillusioned with the prospects for the cur- rent main approach, which uses proteins found on the surface of Plasmodium,the para- site that carries the disease. The best of these vaccines has shown only short-term protec- tion in 40–70% of recipients,indicating that a viable malaria vaccine is still years away. Infected mosquitoes bred in captivity could conceivably deliver an effective vaccine against malaria. So Hoffman is turning to 1967 results from Ruth Nussenzweig’s Institute of Research, both in Sil- from a mosquito injects around 10–20 sporo- group at New York University, ver Spring, Maryland. This shows zoites.So a minimum vaccine dose,equivalent who found that mice could be that humans exposed to more to 1,000 bites, would require at least 104–105 protected from malaria by being than 1,000 bites by infected, irra- sporozoites, to ensure that enough living injected with a form of the para- diated mosquitoes develop over parasites make it to the liver. This is already site — known as a sporozoite — 90% protection against subse- achievable from one mosquito, says Robert extracted from irradiated mos- quent challenges, and that this Sauerwein,head of medical parasitology at the quitoes (R. S. Nussenzweig et al. protection lasts for more than 10 University of Nijmegen in the Netherlands, a 216, 160–162; 1967). The sporo- months (S. L. Hoffman et al. J. collaborator of Hoffman’s. So one mosquito zoites infect the liver in humans Stephen Hoffmann: Infect.Dis.185,1155–1164;2002). could produce one vaccine dose. and provoke an immune back to basics. But the logistical problems This assumes that most sporozoites will response, but, because of the are formidable. “The barriers survive and be immunogenic after storage. If weakening effect of the radiation,they don’t go have seemed sufficiently daunting that no not,many more will be needed.And although on to infect red blood cells or cause malaria. one has been willing to give it a try,” says mosquitoes inject sporozoites into the blood Individually exposing people to thousands Thomas Richie, director of clinical trials at — an efficient route to the liver — intra- of bites by live irradiated mosquitoes is hardly the Naval Medical Research Center Malaria venous vaccine injection is not an option. viable for large-scale immunization.But Hoff- Program in Silver Spring. Hoffman thinks that vaccination under the man claims it should be possible to produce “It’s a long shot,” says Adrian Hill, a skin should be feasible. But the route to the billions of parasites to manufacture a vaccine malaria-vaccine expert at the University of liver would have to be unusually efficient for directly. He intends to breed millions of mos- Oxford, UK: “It’s worth a try, although the this to work. quitoes,grow them on cultures of infected red odds are heavily stacked against him.” Hoffman says that with his initial funding blood cells, dissect out the sporozoites from Hoffman says his work at Celera Genomics he will make sporozoites of clinical-trial the mosquitoes’ salivary glands, purify and on the mosquito genome project helped to quality. If he is successful, a vaccine could be store them,and then find ways of getting them convince him that the obstacles could be over- quickly tested in humans in areas of Africa into people — all under the tough standards of come. He expects to raise $3 million for the where malaria transmission is high. the US Food and Drug Administration. project, including a $550,000 grant from the The plan is the “best show in town” for There is a basis for such a bold project — a National Institutes of Health. malaria vaccines, says Maurice Hilleman, re-analysis of published data by various He will need to produce sufficient numbers director of the Merck Institute for Vaccin- research centres, including the Naval Medical of sporozoites, and to store them in a way that ology in West Point, Pennsylvania.“It might Research Center and the Walter Reed Army retains their ability to infect liver cells. A bite even be the only show in town.” ■ NATURE | VOL 425 | 2 OCTOBER 2003 | www.nature.com/nature © 2003 Nature Publishing Group 437.