A global challenge

The second vaccine focus of Cowman's group is a collaborative effort with laboratories in the US to develop an attenuated vaccine against malaria that targets the liver stage of the disease. Cowman's laboratory developed the ability to knock out P. falciparum genes in 1997, making the possibility of genetically attenuated vaccines a reality.

Subsequently, one of Cowman's collaborators in Seattle identified the key genes that need to be knocked out to block development of the parasite in the liver stage. Without these genes expressed, the Plasmodium develop to a certain point and then stop, meaning that in vivo the malaria parasite still gets transmitted but does not cause disease.

The attenuated vaccine project is at a more advanced stage than the invasion-targeted effort and it is hoped that clinical trials will begin soon at the Walter Reed Army Medical Centre in Washington. The trials will be the first to test a genetically attenuated live parasite in a vaccine.

"We have used genetic manipulation technology over many years to get to this point, and are confident that the attenuated organism will work as it should mechanistically," Cowman says.

"The vaccine has been validated already, both in mouse models and using gamma-irradiated merozoites. The largest obstacle to this type of vaccines now is delivery of a live parasite in developing countries. Storage, handling and distribution of the vaccine - these are all serious logistical problems that need to be overcome if this approach is going to be effective."

Current measures to prevent malaria infection and the spread of disease are still centred on vector control measures and anti-malarial drugs. The distribution of drugs and even insecticide-impregnated bednets in affected areas remains a problem, although much less so now with global funding efforts such as the Gates Foundation and the Malaria Vaccine Initiative.

Although these measures are reducing the local incidence in some endemic areas, development of a vaccine is still a priority. The on-going research commitment of scientists like Cowman therefore remains at the frontline of the continuing battle to prevent malaria infection and improve the lives of so many.