Prevention of Animal Disease Using Genetically Engineered Vaccines

By James A. Weber, Assistant Professor of Animal and Veterinary Sciences, University of Maine

SUMMARY

Genetic engineering has been used to make new, highly effective types of vaccines to protect animals or humans from disease. The approach is to use molecular techniques to "disarm" the pathogen, or to express single proteins of the pathogen in a harmless bacterium or the vaccinated animal itself. These strategies elicit a strong immune response against the pathogen without exposure to the disease-causing organism.

Vaccines are among the most cost-effective weapons in the fight against infectious diseases of animals. By mimicking a disease-causing organism (pathogen) in the body without causing signs of disease, an effective vaccine stimulates the immune system to protect against the disease, often for years after vaccination. Efficacy and safety are the primary considerations in the design of a new vaccine. Killed vaccines have historically been considered as the safest vaccination option available, since they do not replicate in the body. Unfortunately, this characteristic also results in relatively weak immunity to disease. Since most killed vaccines are crude preparations, they sometimes cause unwanted inflammation at the injection site.

In comparison, vaccines composed of active organisms that can replicate in the body elicit a more widespread and long lasting immune response than killed vaccines, and produce a stronger and a longer-lasting immunity. However, their ability to cause disease must be reduced to a safe level by a process known as "attenuation." Until the advent of molecular biology techniques, pathogenic organisms were attenuated by culturing them under unusual conditions. For example, a virus that normally causes disease in mammals would be grown in chicken cells at cool temperatures. Growth under these conditions results in the randomly mutated viruses that have adapted to the artificial conditions but lost the ability to cause disease in the original host. Attenuated live vaccines, because they replicate in the body, elicit a more vigorous and long-lasting immune response than inactivated vaccines. But attenuated vaccines carry the potential risk that the mutation which reduced their ability to cause disease might be reversed by another mutation after injection.

With the advent of molecular techniques, genetically modified organisms have been produced that stimulate strong immunity with few of the risks of earlier vaccines. At present, several different classes of genetically modified vaccines are either in testing or already on the market.

The first approach stimulates an immune response using only a single protein or protein fragment from a pathogen synthesized in genetically engineered cells. An example of this type of vaccine was developed against the bacteria that causes Lyme disease. Molecular techniques were used to specifically amplify the synthesis of a specific bacterial surface protein that stimulates a strong immune response, and the purified single recombinant protein was used an effective vaccine protecting against Lyme disease.

A second type approach is to use genetic engineering to create a "live attenuated vaccine" by specific deletion of genetic information. Removal of this information renders the disease-causing organism harmless by taking away the genes coding for those proteins necessary to cause disease, while preserving the genes for proteins that stimulate the immune system. Because a known, large segment of the pathogen is removed through molecular biology procedures, these vaccines offer the promise of vigorous immune responses with a greatly decreased risk of reverse mutation to a disease-causing organism in comparison to attenuated vaccines.

A third type of genetically-engineered vaccine can be produced by inserting immune-inducing genes from a pathogenic organism into a vector that is not capable of causing disease in the vaccinated animal. For example, a harmless bacterium can be given the genetic information to make a surface protein of a pathogen. Once inoculated into the host, this bacterium will stimulate an immune response against both its own proteins and the surface protein of the disease-causing organism. This approach has great potential as a vaccine because it stimulates cell-mediated as well as humoral (antibody-producing) immunity. Many viral pathogens avoid the humoral immune system by hiding in cells, and can only be destroyed by cell-mediated immune responses. In addition, these types of genetically-engineered vaccines can be administered orally if a bacterium is chosen that can enter the body through the digestive tract. Most traditional vaccines must be injected directly into tissues to elicit an immune response.

A fourth type of vaccination approach is to inject a defined segment of DNA into a patient or an animal. The DNA is chosen to code for one specific antigenic protein from a pathogen. The protein made is chosen to elicit an immune response but not to cause disease. Such "DNA-based vaccines" are similar in principle to the third approach, but rely entirely on the animal’s cells to take up the injected DNA and make the foreign protein. The DNA is incapable of copying itself and thus cannot inadvertently "infect" unvaccinated animals. Early trials with naked DNA vaccines in farm animals have resulted in both humoral and cell-mediated immunity, and it appears that the immune stimulation from one vaccination can persist for months. Initial concerns that the foreign DNA may become incorporated into the host’s chromosomes have not been demonstrated, although the possibility has slowed commercial application.

Most new vaccine development is currently limited to a small number of international pharmaceutical companies. Genetically engineered vaccines offer so many advantages over traditional vaccines that they will gradually replace many currently available vaccines in the next few years. Animals vaccinated with the latter type of genetically-engineered vaccines would be considered transgenic.

For further information, contact:
James A. Weber, Assistant professor
Department of Biosystems Science and Engineering, University of Maine
Phone: 581-2774 or E-mail: jweber@umext.maine.edu