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Vaccine could help control reproduction in livestock, pets

Stepping through the doors into Clark Annex, you get the sense of a well-run farming operation. The dark green and aluminum interior comes complete with a grain bin rising through the ceiling. Jerry Reeves – one of eight research scientists housed here – spends his days appropriately studying ways to improve the ranching industry. Though primarily focused on cattle, his findings may benefit the lives of people and animals worldwide.

Reeves, professor and Baxter endowed chair in the Department of Animal Sciences, is also an associate in the Center for Reproductive Biology. After nearly 20 years of dedicated team effort, he has recently finalized a vaccine to control reproduction in mammals. In Brazilian field trials, Reeves and his team immunized cattle with an anti-LHRH (lutenizing hormone releasing hormone) vaccine – producing 95 percent effective sterilization in bulls. Studies on heifers in the U.S. produced similar results.

Master hormone target
LHRH – produced in the hypothalamus – is a master hormone that acts on the pituitary gland to prompt the release of follicle stimulating hormone (FSH) and lutenizing hormone (LH). These hormones control the production of estrogen and testosterone leading to ovulation in females and sperm development in males. It was Reeves’ theory that creating a vaccine to interrupt the action of LHRH should work universally – on all mammals, male or female.

Unlike vaccines produced against virus or bacteria, however, it is difficult to stimulate antibody defense against a natural hormone like LHRH. To sidestep that problem, Reeves coupled the hormone to the protein in egg white – ovalbumin – hoping to “trick” the body into recognizing it as an intruder.

It worked and test animals produced anti-LHRH antibodies. But because a consistent product could not be guaranteed, neither the U.S. Department of Agriculture nor the Food and Drug Administration would approve the vaccine.

Undaunted, Reeves and his team turned to genetic engineering. With the help of Kevin Bertrand, formerly with the School of Molecular Biosciences, they combined genes from both LHRH and ovalbumin to create a new type of DNA. This DNA was inserted into E.coli bacteria which, like tiny manufacturing plants, mass-produced a purified “fusion protein” called ovalbumin-LHRH-7. The protein was combined with an immune-boosting agent (adjuvant) and injected into animals as a vaccine.

“So far, this protein has worked very well,” said Reeves. “It has produced antibodies in cattle, rats, mice, pigs, sheep, cats and dogs. It removes naturally occurring LHRH from the animal and prevents FSH/LH release, resulting in “immunoneutering.”

Feral dog and cat control
Reeves –  together with Bertrand and former Ph.D. student Yuzhi Zhang – holds two patents through WSU for the LHRH vaccine, which has been licensed to Amplicon Express, a molecular biology service provider in Pullman. Due to prohibitive costs, it is unlikely the vaccine will be approved for use in U.S. food-chain animals any time soon, but it could be introduced for feral dogs and cats in the near future.

“Our primary focus will be on control of wild dog and cat populations worldwide,” said Bert Bogden of Amplicon Express. “Our key challenge right now is to produce a vaccine that will work with only one injection – currently two or more injections are needed to cause sterilization. We hope to have a product on the U.S. market within 18 months and on the international market – Mexico and Brazil – within a year,” he said.

The company also is considering market opportunities for use in bulls in Brazil and lambs in the Middle East.

“There has been widespread interest in the vaccine for everything from contraceptives to treating prostate cancer to treating overpopulated herds of elephants in Africa,” said Reeves.

Immunocastration a successful alternative
In a study funded by the Washington Technology Center and Amplicon Express, Jerry Reeves, professor and Baxter endowed chair in the Department of Animal Sciences, and Jennifer Hernandez, his Ph.D. student, took their fledgling LHRH vaccine to Brazil to conduct “immunocastration” field trials on bulls.

Unlike the U.S, Brazil – the second largest cattle producing country in the world – does not permit the use of steroid hormone implants to increase growth. Instead, ranchers prefer to let bulls grow on pasture for two years before castrating them. They are then allowed to grow another year- as steers – before they are butchered.

But castration of large bulls in the tropics often can be traumatic and may result in death.

As an alternative to physical castration, Reeves offered to test the LHRH vaccine on two large cattle ranches in the state of Moto Grosso in 2005. The study was carried out in collaboration with Eraldo Zanella from the Universidade de Passo Fundo.

Vaccination results showed conclusively that as antibody levels rose in the bulls, testosterone levels dropped along with other parameters such as scrotal size and body weight. At the same time, body fat and marbling of the meat increased to match that of the steers. The vaccine proved to be a successful and humane alternative to physical castration.

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