In a study reported today in the Proceedings of the National Academy of Sciences online, researchers developed mice that could secrete an experimental malaria vaccine into their milk.

When the purified candidate vaccine was injected into monkeys, it protected four out of five animals from a lethal dose of the malaria parasite. If the process can be scaled up to larger animals such as goats -- and early experiments indicate it can -- livestock might prove to be inexpensive, high-yield malaria vaccine factories.

"A vaccine must not only be effective, it must be cheap to manufacture if it is to be used in those countries hit hardest by malaria," says lead author Anthony Stowers, Ph.D., a malaria researcher at the National Institute of Allergy and Infectious Diseases (NIAID). "Using 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."

Transgenic animals are so named because they contain a gene, called a transgene, from another individual or organism. For years transgenic animals, particularly mice, have been used to help scientists understand how genes work and interact with one another. More recently, researchers have introduced genes encoding specific proteins into animals to produce large quantities of those proteins for medical use. Dr. Stowers and his colleagues investigated whether transgenic animals could produce proteins for use in malaria vaccines.

Dr. Stowers and Louis Miller, M.D., chief of NIAID's Laboratory of Parasitic Diseases and the director of its Malaria Vaccine Development Unit, joined other investigators from NIAID and Genzyme Transgenics Corporation, Framingham, Mass., to produce two transgenic mouse strains. Each strain carried a form of the gene for a surface protein from the deadliest malaria parasite, Plasmodium falciparum. The researchers designed the transgenes to be switched on by the cells that line the mammary glands, such that the resulting proteins would be secreted into the animals' milk.

Both mouse strains produced large quantities of the desired vaccine protein, which was used to vaccinate monkeys against malaria. Only one of the five immunized animals contracted the disease. By comparison, six out of seven unvaccinated animals had to be treated for virulent malaria.

The high yield of the protein and its ability to stimulate protective immunity in mice offers promising evidence that the technique could also be used in goats or even cows. The researchers had anticipated future studies in goats by designing the transgenes' on/off switch using regulatory elements from goat DNA.

Preliminary experiments, which have not yet been published, suggest the procedure works well in the larger animals. That possibility offers a far more practical option for large-scale vaccine production.

Anthony S. Fauci, M.D., who as NIAID director guides an extensive research program on global infectious diseases, believes this approach is promising. "Malaria causes untold suffering in the poorest regions of the world, so we cannot restrict our focus simply to finding a vaccine that works," he says. "Rather, we must look for innovative strategies that will bring effective vaccines to regions where economic conditions preclude the use of costly alternatives. Transgenic animals could be one way to accomplish that goal."

The study involved many researchers from the two participating institutions. Among these, Drs. Li-How Chen and Harry Meade directed the studies conducted at Genzyme Transgenics. B. Fenton Hall, M.D., from NIAID's Parasitology and International Programs Branch, also helped initiate the project and played an active role in its development.

NIAID is a component of the National Institutes of Health (NIH). NIAID supports basic and applied research to prevent, diagnose, and treat infectious and immune-mediated illnesses, including HIV/AIDS and other sexually transmitted diseases, tuberculosis, malaria, autoimmune disorders, asthma and allergies. - By Sam Perdue

(Reference: AW Stowers et al. A recombinant vaccine expressed in milk of transgenic mice protects Aotus monkeys from lethal challenge with Plasmodium falciparum. Proceedings of the National Academy of Sciences Early Edition online December 17, 2001.)

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[Contact: Sam Perdue ]

18-Dec-2001