National Wildlife Research Center (NWRC) |
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| Development of Reproductive
Control Methods for
*Information below is also available in a downloadable PDF document, "GnRH Deer Population Control." 161K Introduction In fall, as daylength decreases, reproductive systems in many mammalian species that occupy temperate habitats "turn on." Testosterone levels rise in males, and females begin estrous cycling (“going into heat”). Gonadotropin-releasing hormone (GnRH) is part of a pathway that signals the body to produce sex hormones. GnRH is produced by the hypothalamus, a major organ in the brain. Without GnRH, very little estrogen, progesterone, or testosterone are made. The aim of a GnRH vaccine is to bind to or “tie up” the GnRH produced within an animal's body so that it does not trigger reproduction. The vaccine induces the body to make antibodies against its own GnRH. To do this, GnRH is synthesized and hooked to a foreign protein. This new material (called a conjugate because it is made up of two components) looks like a giant new molecule that the animal's immune system has never encountered. As a result, when the GnRH vaccine is injected into the animal's body, the body's immune response neutralizes the hormone's function, resulting in infertility in both males and females. As part of its program to develop tools for managing populations of overabundant wildlife species, NWRC scientists have developed a new GnRH immunocontraceptive vaccine (named GonaCon™) that shows great promise as a wildlife infertility agent. (Technical discussion on how GnRH immunocontraception works) Two major obstacles had to be overcome during the development of this vaccine. First, a new adjuvant had to be developed (an adjuvant is a compound that improves the immune response, causing higher levels of antibodies). A replacement for the commonly used Freund’s adjuvant was needed because the U.S. Food and Drug Administration (FDA) has objected to its use. Accordingly, NWRC scientists developed a new adjuvant (called AdjuVac™) that is more effective than Freund’s adjuvant but lacks the negative side effects. (More on AdjuVac™ development) The second major obstacle to the development of a new immunocontraceptive vaccine for wildlife was the need for a single-dose contraceptive, because of the impracticality of capturing free-ranging wild animals twice to vaccinate them. Previous contraceptive vaccines required at least two injections (an initial dose followed by a booster dose). Although it was originally developed as a two-injection contraceptive treatment, NWRC’s GnRH (gonadotropin-releasing hormone) vaccine was subsequently tested in a single-injection form that is much more practical as a field delivery system. Development of the single-injection vaccine was possible only because of the creation of AdjuVac™ adjuvant. The usefulness of a single-shot immunocontraceptive vaccine depends, among other things, on the duration of the contraceptive effect that the vaccine produces. The combination of AdjuVac™ adjuvant and NWRC’s GnRH conjugate produces a much longer-lasting contraceptive effect than was produced by earlier efforts that combined Freund’s adjuvant with the (same) GnRH conjugate. (Technical discussion of NWRC vaccine conjugate design) Pen and Field Studies of GonaCon™ Recent studies with free-ranging California ground squirrels, captive Norway rats, domestic and feral swine, wild horses, and white-tailed deer have demonstrated the efficacy of the single-shot GnRH vaccine as a contraceptive agent. Infertility among treated female swine and white-tailed deer, for example, lasted up to two years without requiring a booster vaccination. Ongoing studies are examining the practicality of administering GonaCon™ to free-ranging white-tailed deer as well as the efficacy, toxicity, and safety of the vaccine. Pivotal field studies underway in Maryland and New Jersey are evaluating the efficacy of GonaCon™ as a contraceptive agent for free-ranging female white-tailed deer under field conditions. In Maryland, an overpopulated deer herd on a completely fenced site was initially reduced in density by Wildlife Services sharpshooters at the request of property owners. Once the population size was reduced to a level that could be supported by the available habitat, contraception was applied to adult females. Forty does were captured, marked, and released at their capture sites during July 2004. Of these 40 does, 25 were injected with GonaCon™ vaccine, and 15 were maintained as unvaccinated control animals. Field observations during summer 2005 indicated that only 3 (12%) of the 25 GonaCon™-treated does produced fawns in 2005, whereas 10 (83%) of 12 control does for which conclusive data are available bore fawns. The Maryland deer study will continue through fall 2006. NWRC scientists are working closely with Maryland Wildlife Services to complete this field study. A second pivotal field study of GonaCon™ vaccine as a contraceptive for white-tailed deer was begun in a privately-owned corporate office park in central New Jersey in July 2005. Traffic hazards and extensive damage to vegetation were being caused by overabundant deer on this fully enclosed (fenced) property. During July and August 2005, all 43 adult does present on the site were captured, marked, given injections, and released. Twenty-nine of these does received GonaCon™ vaccine, and the remaining 14 were given sham injections. Reproductive success of the 43 does will be documented for two years to determine the effectiveness of GonaCon™ vaccine as an infertility agent. NWRC scientists are collaborating on this field study with White Buffalo, Inc., a non-profit, Connecticut-based research organization dedicated to conserving ecosystems through wildlife population control. In a nearly completed study of captive white-tailed deer at Pennsylvania State University, research was designed to assess the toxicity and safety of GonaCon™. Responses of treated and control groups of deer are being compared via analyses that include blood chemistry, hematology, and histopathology, as well as assays of circulating progesterone, luteinizing hormone, and GnRH antibodies. Preliminary analyses indicate that no toxicity or safety problems are associated with the use of GonaCon™ vaccine. Analyses will soon be completed and a final report will be submitted to the FDA. The Pennsylvania captive deer study is being conducted cooperatively by scientists from NWRC and Pennsylvania State University. FDA Registration of GonaCon™ No fertility control agents have been approved by the FDA for non-investigational use on wildlife populations in the United States. Several materials, however, including GnRH and PZP vaccines, have been classified as investigational drugs that may be used (only) in rigidly-controlled research studies. The 3 GonaCon™ studies underway in Maryland, New Jersey, and Pennsylvania are being conducted as pivotal studies that are required as part of the FDA’s approval process for a New Animal Drug. The approval process for GonaCon™ vaccine began in 1998 when the FDA established an Investigational New Animal Drug (INAD) exemption for the GnRH vaccine. All research studies of GnRH vaccine have been conducted under this exemption (INAD – 10006). A development plan for GonaCon™ was prepared by NWRC staff during June 2004. The plan provides guidance for NWRC’s efforts to take the immunocontraceptive vaccine to market. Advantages of GnRH NWRC scientists are hopeful that the GnRH vaccine will soon be developed and approved for use for wildlife fertility control. GnRH vaccines have an advantage over PZP because they prevent eggs from being released from the ovaries, thereby eliminating estrus and some undesirable behaviors (e.g., bucks chasing does across roads) associated with it. In addition, GnRH vaccine has promise for reducing or eliminating certain undesirable behaviors in companion animals. For example, fighting, scent-marking, caterwauling, and wandering by cats, and unruly behavior in horses, could be reduced by GnRH vaccine because the vaccine indirectly blocks the production of sex hormones (e.g., estrogen and testosterone) which contribute to the expression of such behaviors. The single-shot, multi-year GonaCon™ vaccine will be a useful technique for the management of certain enclosed or urban/suburban wildlife populations, such as deer. GonaCon™ still has limitations, however, especially the need to capture and inject each animal. NWRC scientists hope to eventually produce an oral GnRH vaccine that will be attractive to the target species but will be unlikely to be consumed by nontarget animals. GonaCon™--Birth Control for Deer: Questions and Answers Project
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Last Modified: January 9, 2008