A malaria vaccine purified from milk produced by genetically modified mice successfully protects monkeys against the disease, say US researchers. The team have also modified goats to excrete the protein in their milk, raising the prospect of a cheap way to mass-produce a malaria vaccine to save millions of lives each year.
鈥淎 vaccine must not only be effective, it must be cheap to manufacture if it is to be used in those countries hardest hit by malaria,鈥 says Anthony Stowers of the US National Institute of Allergy and Infectious Disease, who directed the new research in collaboration with biotech company Genzyme.
鈥淯sing transgenic animals to achieve both ends is an exciting possibility. If it works, a herd of several goats could conceivably produce enough vaccine for all of Africa,鈥 he says.
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Clinical trials using the milk-derived vaccine on people could begin in 2003, Stowers says. But he thinks the existing vaccine will have to be modified to include more proteins to produce effective protection in the field.
Regina Rabinovich, director of the US-based Malaria Vaccine Initiative, says the results are 鈥渧ery encouraging鈥. However, she warns that it is very hard to model malaria infection in animals. 鈥淲e won鈥檛 really know how useful this is until some formulation is tested in human trials,鈥 she says.
Deadliest parasite
Genzyme created a strain of mice carrying a form of the gene for a surface protein from the deadliest malaria parasite, Plasmodium falciparum. The gene was designed to be switched on by cells that line the mammary glands, so the protein, called MSP142, would be secreted into the animals鈥 milk.
The researchers found that the mouse milk contained very high levels of MSP142. 鈥淲e got the equivalent of 900 milligrammes per litre 鈥 and we鈥檇 be talking about vaccinating a person with about 25 microgrammes,鈥 Stowers says.
The team then studied the effectiveness of the purified vaccine on 12 Aotus nancymai monkeys 鈥 a species that is susceptible to lethal infection with the P. falciparum parasite. Only one of five immunised animals contracted the disease. But six out of seven unvaccinated monkeys had to be treated for virulent malaria.
鈥淚n terms of the protection induced in the monkey malaria models, our vaccine is one of the best,鈥 Stowers says.
It is possible to produce relatively small amounts of the vaccine using a standard lab technique. 鈥淏ut this is a fairly complex, expensive methodology,鈥 Stowers adds.
Goat vaccine
Initial tests on a modified herd of goats created by Genzyme shows that they also produce high levels of the protein in their milk. The team will now try the goat-milk-derived vaccine in monkeys.
Several teams around the world are working on experimental malaria vaccines. The most clinically advanced was developed by pharmaceutical giant GlaxoSmithKline, using standard laboratory techniques. This vaccine recently showed promising results in a field trial in Gambia.
But since malaria kills people in predominantly the poorest parts of the world, malaria researchers must strive find a vaccine that not only works, but is cheap, says Rabinovich. 鈥淭he production of the protein in goats鈥 milk is potentially a very efficient, scalable and cost-effective production system,鈥 she says.
Journal reference: Proceedings of the National Academy of Sciences, early edition (DOI: 10.1073/pnas.012590199)