New Vaccines for Old Diseases

Kenneth J. Cremer, associate program manager, Biotechnology Competitive Research Grants Office, Office of Grants and Program Systems.

Opportunities for advances that will improve livestock productivity are greater today than ever before through the powerful new products of the biotechnological process. Each year, because of disease, the productivity of livestock and poultry in the United States is reduced by an estimated 15 to 20 percent. Investigations show that many animal diseases can be controlled by combinations of procedures, such as improved diagnosis, control of the insect carriers of disease, vaccination of susceptible animals, enhancement of the immune system, and improved therapy.

Most vaccines against pathogenic (disease-producing) organisms of viral, bacterial, fungal, or parasitic origin consist of the organism being either killed or chemically weakened or genetically modified to reduce its virulence. The animal's immune system responds to vaccines by producing antibodies that bind to antigens or surface structures of the infecting organism, labeling it for attack and destruction by the immune system. Antibodies produced in response to the modified or killed pathogen circulate throughout the animal's body and render the animal resistant to later infections by the live pathogenic organism.

Lesions on a cow's tongue show the presence of vesicular stomatitis virus.

Vaccinia Virus Vectors

During the last few years, several groups of U.S. scientists have designed vaccine vectors (carriers) that may someday be universally used to safely vaccinate a variety of animal species against a number of infectious agents. Vaccinia virus vaccines were used extensively worldwide during the smallpox eradication campaign 10 to 20 years ago. These same smallpox vaccines have recently been genetically engineered to express foreign proteins from different disease-causing organisms, allowing their potential use as vaccine vectors for domestic animals as well humans. The genetically modified vaccinia virus grows in most animal species and can be engineered to express one or more foreign protein antigens, thus increasing their general utility and potential effectiveness.

The use of modified, weakened live viruses to stimulate immune responses exemplifies the exciting and powerful recent advances in applying genetic engineering and recombinant DNA technologies to the problems of control and eradication of infectious diseases in domestic animals, both in the West and Third World countries.

Vesicular Stomatitis Virus

Vesicular stomatitis virus (VSV) is a highly contagious disease of cattle, horses, and pigs, characterized by vesicular lesions on the tongue and other areas inside the mouth. The lesions are similar to those seen in animals infected with foot-and-mouth disease, another highly contagious and fatal cattle disease. Humans also are susceptible to VSV, and exhibit influenza-like symptoms. Outbreaks of VSV have been devastating to the livestock industry, as exemplified by a recent epizootic outbreak in 13 Western States.

VSV has five distinct proteins, only one of which, the G-glycoprotein, has been shown to promote protective immunity. Vaccinia virus has recently been genetically engineered to express the VSV G-glycoprotein. Experiments recently completed with this vaccine indicated that immunity to the G protein was induced in vaccinated cattle. It effectively protected animals from a controlled infection by VSV under laboratory conditions, whereas unvaccinated animals were susceptible to mouth infection of VSV. Field trials are planned to determine this vaccine's effectiveness in a natural setting.

Bluetongue Virus

Bluetongue (BTV) is an arthropod-transmitted viral disease of both domestic and wild ruminants in the United States, Asia, Australia, Europe, and Africa. The virus can be transmitted between cattle and sheep by gnats.

The disease is characterized by fever, erosion, and ulceration inside the nose, lameness, weight loss, and eventual death of some infected animals. Direct losses from subclinical disease, fetal death or abortion, and the hazards of animals introducing the infection to a susceptible flock or herd are well appreciated by ranchers and veterinarians. A segment of the bluetongue virus genome (set of chromosomes with genes) has been cloned recently. Construction of a recombinant vaccinia virus expressing one of the BTV capsid structural proteins is under way. Limited experimental trials of the recombinant virus under controlled conditions are contemplated for the near future.