What if an injectible vaccine were available to sterilize bull calves or suppress estrus in heifers? Researchers in the U.S. are developing such a non-invasive tool to block the hormone production sequences that cause the growth of gonadal tissue (testes or ovaries) in cattle. Thus, there's no sperm production in males or ovulation in females.
Similar “castration vaccination” work is underway in Canada where a vaccine has been tested at the Lethbridge Research Centre in Alberta.
The concept of using antibodies to neutralize hormones has been around since the late 1950s when antibody production was used to control insulin in humans. But, thus far, vaccines that inhibit reproduction in animals have been more effective in pigs and sheep than in cattle.
“That's primarily because cattle's immune systems seem more resistant to the vaccine,” says Tom Adams, a University of California-Davis (UC-Davis) animal science professor who's developing a vaccine to inhibit gonadotropin-releasing hormone (GnRH) production in cattle. “It's difficult to get an antibody level high enough to completely shut down bovine reproductive function,” he says.
GnRH normally triggers other hormones to produce testosterone in males and estrogen in females.
“In our studies, we had the greatest success when we administered the primary immunization at about three months of age, followed by a booster at feedlot entry at about one year of age,” Adams says.
With a primary vaccination and a booster several months later, testosterone levels stay low from feedlot entry until harvest, assuming the cattle are harvested at 18 months of age or earlier, he reports.
Adams led a study in which the objective was to delay puberty in heifers so they wouldn't become pregnant before they were mature enough to carry a pregnancy.
“In that study, we gave only a primary immunization. It delayed puberty, but the animals eventually began to cycle, ovulate and became pregnant,” he says. “So, it was effective in blocking reproductive function but not eliminating it.”
One disadvantage to the UC-Davis vaccine is that it's not a patentable process. And, without an exclusive right to the process, Adams says vaccine companies generally aren't interested in marketing such products.
Different Vaccine Products
Washington State University (WSU) has two U.S. patents on a luteinizing hormone-releasing hormone sterilization vaccine. A small Washington biotech company, Amplicon Express, and a sister company in France, have the licensing rights from WSU.
Evaluations of the WSU vaccine on two cattle ranches in Brazil have found more than 95% effectiveness while carcass value increased in the Nelore-based test herds.
“It's our opinion this can be a very important approach to control growth, nutrient utilization and reproductive efficiency in the future,” says Jerry Reeves, WSU professor and animal scientist. “However, these vaccines need to be more than 95% effective if they're to be accepted as sterilization vaccines.”
USDA awarded Reeves' lab a $250,000 grant to study the potential of WSU's sterilization vaccine in heifers. The LHRH vaccine could be a possible replacement for melengestrol acetate (MGA) in the feedlot to suppress estrus.
Recombinant Protein
Adams says a major difference of the Canadian vaccination product being tested in Lethbridge is that it uses a protein synthesized in bacteria recombinant (new combination) protein. The UC-Davis product utilizes a naturally occurring protein.
“Our work clearly demonstrates that vaccination against GnRH has considerable potential as an alternative to traditional methods,” says John Kastelic, a veterinarian and reproductive physiologist at the Lethbridge Research Centre.
“The vaccine itself is superb,” Kastelic says. “We got great results in testing, and its design is really unique and so effective.” He says the commercial version of the vaccine has thus far been kept on the laboratory shelf by expense and regulatory hurdles.
There have also been problems with the adjuvant needed to deliver the genetically modified vaccine. But, Kastelic predicts the product could become available to Canadian producers within a few years.
Overall, there's growing interest in immunization castration. The interest comes not only from cattlemen but folks who want to control reproduction in wild animals and companion animals, Adams says.
More Effective, Less Risky
The UC-Davis vaccine has proven to be more effective in suppressing estrus in heifers than MGA, Adams says, adding, “It's less risky than spaying.”
The drawback to the Canadian vaccine and other recombinant proteins is that they're not as immunogenic as the naturally occurring proteins like those UC-Davis uses in its vaccine. The immunization process involves injecting an antigen — such as a foreign protein — into the body.
“But, we also face a problem with GnRH because it's not foreign. It's a naturally occurring hormone,” Adams adds. Thus, the body has difficulty developing immunity to its own protein, he says.
One way to get around this, Adams says, is to link GnRH to a larger carrier protein that has known immunogenicity through conjugation. The body can recognize the conjugated product as foreign and will develop antibodies against it.
“That's one of the advantages of the UC-Davis process,” Adams says.
But, the Canadian system generates proteins using molecular biological techniques — “a twist that makes their system possibly patentable, whereas ours is not,” says Adams.
A More Humane Alternative?
Adams says the primary impetus for his team's work is the animal rights/animal welfare issue.
“With animal rights and welfare groups demanding more humane management techniques, cattlemen may eventually be forced to forego traditional methods of castration,” Adams says. “We want to give cattlemen an alternative that wouldn't affect production, growth or carcass quality.”
Although the UC-Davis work isn't eligible for patent, it demonstrates that vaccination is an effective procedure, Adams says.
“We're waiting for a company to come along that can generate a patentable vaccine that's as effective as the chemically synthesized vaccine,” he says.
These products may take time to reach the U.S. market due to Food and Drug Administration (FDA) requirements. Because immunization products differ in function from traditional disease vaccines, they are regulated by FDA rather than USDA.
FDA has two primary criteria for these types of products:
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The drug (vaccine) does what it is supposed to do; and
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The resulting animal is safe for human consumption.
In judging whether a vaccine is safe, FDA requires that the exact molecular structure of the product be known and that it stays the same batch to batch, Reeves says.
“With our present knowledge of chemical conjugation procedures, which are quite sophisticated, it's still virtually impossible to ensure that the exact structure is the same from batch to batch,” he says.
Reeves believes consumer pressure will force changes in some industry production practices and that these types of vaccines will help. “But, today, it is still the most practical to castrate bull calves with a sharp knife as practiced by most commercial cattlemen,” he says.
Heather Smith Thomas is a freelance writer based in Salmon, ID. Clint Peck is BEEF senior editor.
Trials With Bulls, Steers and Heifers
University of California-Davis (UC-Davis) trials of a vaccine to immunize against gonadotropin-releasing hormone (GnRH) in feedlot cattle shows the best results come with a primary vaccination at 3-7 months of age and a booster at feedlot entry.
Feeding performance of young bulls was significantly lowered by castration but not by immunization against GnRH. Using vaccination instead of castration reduced the need for implants, researchers found. Residual levels of testosterone secretion in immunized bulls may have anabolic effects.
Bull calves vaccinated at 3-4 months of age all developed significant titer against GnRH by weaning time, and titer remained high until slaughter. In calves given a booster vaccination at feedlot entry, titer was greatly increased 4 weeks later, but returned to pre-booster levels within 12 weeks. If calves are to receive only one vaccination, it works best if given at about 7 months of age.
Feedlot performance (final live weight and rate of gain) of immunized bulls was comparable to intact bulls. But, the immunized bulls had improved carcass quality and less aggressive behavior.
Carcass quality from steers and immunized bulls was significantly better than that of carcasses from control bulls.
Muscle mass was similar in implanted steers and immunized bulls. In contrast, muscle mass and dressing percentage were significantly less in non-implanted steers.
Marbling was comparable in steers and immunized bulls. Animals with the least marbling were the intact control bulls.
Researchers found that vaccination of heifers against GnRH effectively suppressed their reproductive activity. In addition, they found the lower weight gain that accompanies such suppression can be reversed by use of implants containing anabolic steroids.
Feed efficiency and weight gain during the final weeks were slightly improved in vaccinated heifers and MGA-fed heifers, compared to heifers in the control groups.
Among 48 heifers exposed to bulls but not vaccinated against GnRH, 40 were pregnant (83.3%). In contrast, only four of 48 heifers in the vaccinated group were pregnant at harvest.
Feedlot gain did not differ much between test groups, but dressing percentage and muscle mass were reduced (and marbling and quality grade increased) in the pregnant heifers. Heifers immunized against GnRH had carcass characteristics intermediate between those of the pregnant and non-pregnant controls.
