A genetically engineered vaccine aimed at eradicating a devastating cattle disease in Africa and Asia has been further improved in the laboratory by the virologist and colleagues who first developed the vaccine at the University of California, Davis. The method for producing the recombinant DNA vaccine will be reported in the Sept. 15 issue of the Proceedings of the National Academy of Sciences by researchers at the UC Davis School of Veterinary Medicine and at the U.S. Department of Agriculture's Plum Island Animal Disease Center in New York. The vaccine is directed at rinderpest, a highly contagious viral disease that is more than 95 percent fatal in cattle, buffalo and other ruminants. Rinderpest -- which means cattle plague in German -- attacks the animal's gut and causes bloody diarrhea and pneumonia. It was common among cattle of ancient Europe, but is now confined to developing nations of Africa and Asia where it has killed more than 2 million cattle and buffalo annually. The University of California has filed for a patent on the procedure for making this double recombinant vaccine. In 1988, a team of researchers led by Dr. Tilahun Yilma, a native of Ethiopia and professor of microbiology and immunology in UC Davis' veterinary school, reported in the journal Science the development of a recombinant vaccine with the potential for eradicating rinderpest worldwide. The vaccine was made by individually inserting two genes into the vaccinia virus, the same virus used for the smallpox vaccination. Both the hemaglutinan (HA) and the fusion (F) genes are needed to stimulate an immune response to rinderpest in the vaccinated animal. The recombinant viruses, carrying one or the other gene, were then mixed into a single vaccine. When tested under laboratory conditions, that original vaccine proved to be a practical, effective method for dealing with rinderpest. It did not require refrigeration and a scab removed from a vaccinated calf could be used to produce more than 300,000 doses of the vaccine. Now, however, Yilma and colleagues have taken the work one step further by inserting both the HA and F genes directly into a single virus, simplifying the vaccine's production. The new vaccine is equally effective in laboratory tests, protecting cattle that were inoculated with 1,000 times the lethal dose of the rinderpest virus. Researchers serendipitously discovered that the virus contained in the new vaccine has been weakened to the extent that it does not cause the pock mark on the skin that is characteristic of the vaccinia virus, according to Yilma. The absence of these pock lesions almost eliminates the chance that the weakened virus contained in the vaccine could be transmitted from vaccinated animals to humans. This is of particular concern in many African nations where there is a high incidence of acquired immunodeficiency syndrome (AIDS), since humans who carry the AIDS virus are especially vulnerable to other diseases because their immune systems are weakened. "If we succeed in our efforts to eradicate rinderpest, we will not only eliminate the disease, but also open up the international cattle market that is so important to these developing nations," Yilma said. "And without the threat of rinderpest, nomadic peoples will no longer feel the need to raise such large herds of cattle, which are extremely destructive to the environment." Yilma collaborated on this work with Luis Giavedoni and Leslie Jones of the UC Davis Laboratory of Molecular Biology for Tropical Disease Agents and with Charles Mebus of the USDA's Plum Island Animal Disease Center in New York, where they tested the new recombinant vaccine. They now plan to field test the vaccine in Ethiopia, India, Kenya and Egypt. Development of the new vaccine was funded by the Food and Agriculture Organization (FAO) of the United Nations and by the U.S. Agency for International Development (AID).