The physiology of immunocastration in pigs

In 2011 the FDA approved Improvest for commercial use. The product itself is a sterile solution containing natural gonadotropin releasing factor (GnRF) conjugated to diphtheria toxoid in an adjuvanted formulation.
By Michael Fielding on 2/23/2015

Among its myriad benefits, from better feed conversion to improved meat quality, immunocastration in male pigs as an alternative to physical castration has become the clarion call in Europe with consumers calling for changes to animal welfare.
In the United States it was approved for commercial use by the U.S. Food and Drug Administration just four years ago. Zoetis, the animal health company that makes Improvest and its global brand Improvac, is highlighting its environmental impacts and its ability to control both aggression and boar taint, the offensive odor created when pork is cooked. 
Since feed makes up about 60 percent of the cost of raising a hog to market weight, the improved feed conversion (and related reductions in manure and water usage) with immunocastrated barrows helps keep costs down for producers.
Regardless of how it's marketed, though, immunocastration is a novel technology that has brought global pork production to a crossroads.
“Vaccines tell the immune system to produce antibodies in response to disease,” says veterinarian Larry Rueff, whose Indiana-based consultancy Swine Veterinary Services oversees the health programs of farms that have an annual production of approximately 2 million pigs annually. He contracts with Zoetis at its 500-head nursery-to-finishing facility in Greensburg, Ind., where for the past year he has overseen the care and feeding of the pigs owned by Zoetis.
“In this case we’re using the immune system to prevent production of hormones that the body naturally produces. We’re allowing the immune system to naturally shut down the signals that would produce androstenone and skatole, which cause boar taint,” Rueff says.
Physiology from first injection through slaughter

Skatole is produced by bacteria in the intestine of all pigs.
In the pig, the hypothalamus produces a hormone, GnRF. It travels through the blood to the pituitary, which triggers the secretion of the Luteinizing hormone (LH) and follicle-stimulating hormone (FSH), called gonadotropins because they stimulate the testes to produce testosterone and a phermone (androstenone). Skatole is produced by bacteria in the intestine of all pigs, and it not efficiently removed from the pig in the presence of testosterone.
In immunocastrated pigs, the immune system creates an antibody against GnRF, stopping the release of LH and FSH, which in turn fail to signal the testicle to produce testosterone and androstenone. In the absence of testosterone, the pig efficiently removes skatole.
The pig’s body identifies the foreign protein as an antigen. Various types of cells respond, triggering the production of antibodies. The immune system responds by creating an antibody against GnRF – halting the release of LH and FSH, and thereby preventing the release of testosterone and the subsequent release of skatole and androstenone.
“You can block it at any of those steps in the process, but this product blocks GnRF,” says John McGlone, professor of swine, animal behavior and animal welfare at Texas Tech University, who in 1988 authored the industry’s first scientific paper related to the pain of castration. "Scientists have made antibodies to block both LH and testosterone, but blocking GnRF has proven more effective."
The entire process of immunocastration occurs in the brain; it is the absence of testosterone that results in the absence of boar taint. It also is not permanent. For those reasons users of the technology refuse to call it chemical castration, insisting instead on immunocastraion.
Injecting a substance designed to bind the androstenone to stop the process is considered chemical castration; that molecule – the androstenone bound with the injected substance – would travel throughout the body, eventually attaching itself to the testosterone – and ultimately the muscle.
With immunocastration, the antibody doesn’t bind to anything except to the GnRF in the brain. There, the body recognizes the vaccine’s foreign protein molecule as an antigen, tricking the immune system into making the antibody to fight it.
The first dose is administered no earlier than 9 weeks of age (when the hypothalamus and pituitary begin to mount a respone to it). That priming dose triggers the body’s memory system to create the onslaught of antigens when the second dose is administered.
Immunocastration is not permanent because males are consistently producing hormones, and from that fertile spermatozoa. The synthetic protein in the product acts as an immunization against GnRF – similar to a rabies vaccination in other animals. Those vaccines need boosters to keep them active. “You induce an antibody response for a particular period of time,” Rueff explains.
This temporary response – typical of immunizations – wears off after about 10 weeks, according to Zoetis.
Multiple factors affect the immune response, including age, immune system health and whether the product was administered intravenously or subcutaneously.
Concerns over human ingestion

All the activity occurs in the brain to target the organ to produce the appropriate hormones. In this case, that target organ is the testicle. If the messaging to the testicle is shut off, that organ simply doesn’t produce androstenone (above).
Both the FDA and the European Union’s regulatory authority have reported that pork from immunocastrated pigs does not contain any potentially harmful residues and that the consumption of the product "poses no risk to the consumer," according to the European Medicines Agency.
But European consumers (and even some American producers) have expressed concern over the consequences of accidental human injection. Considering that the pig’s DNA is very similar to that of humans – for example, the protein coding sequence – the question arises: Is it possible for a technician to compromise his own reproductive system?
The short answer is: Yes.
To be clear, immunocastration only works via injection. So if ingested (such as through water or food), the body – both pig and human – would digest it as any other protein.
Like any other vaccine, Improvest works with the immune system to tell the body to make antibodies. In the case of immunocastration, those antibodies bind to GnRF in the brain. That chain reaction begins not with the priming dose but rather the second dose.
The body does not produce sufficient antibodies until the second dose, when it responds with heavy production of antibodies that bind to and neutralize GnRF in the bloodstream.
It’s for that reason that Zoetis has required that only trained, certified technicians are allowed to administer the product. It’s also for that reason that technicians are prohibited from administering the product in the future if they have been accidentally injected.
The process involves a safety applicator gun that hides the needle until injection [see video above]. Until the safety trigger is squeezed and the applicator is placed against the neck of the pig, the needle remains inside the applicator. “That needle is never exposed at any time … as [the technician] maneuvers around the pen,” explains Bill Beckman, St, Louis-based area application manager for Zoetis.
Distinguishing between behaviors
Zoetis trains workers to distinguish between sexual behavior (thrusting, rubbing flanks, chasing other pigs around the pen) and playful learned behavior – which even physically castrated barrows and gilts exhibit. “If an untrained person in the barn were to witness that, he may say the hog needs a QA dose when he really doesn’t. The behavior is more curiosity than anything,” Beckman adds.
“As hogs maneuver about the pen, you’re causing a lot of disruption giving the injection. At the last second one could move out of the way and maybe you weren’t sure you got a good dose,” he says. “If you don’t think he got a full dose, go ahead and give him another dose. Since it takes two doses for the product to be effective anyway, you’ll end up giving the hog a quality assurance dose because you missed this one.”
And since feed makes up about 60 percent of the cost of raising a hog to market weight, the improved feed conversion with immunocastrated barrows helps keep costs down for producers.
“Immunocastration provides extra time between puberty and becoming a barrow, so the pigs behave like boars both behaviorally and growth-wise,” explains Gail Golab, director of the Animal Welfare Division at the American Veterinary Medical Association. “Physically castrated barrows never have the opportunity for a growth rate like an intact. Immunocastrated pigs grow better."