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The purpose of this study was to determine if the number of pregnancies in naturally infected Brucella abortus–positive bison (Bison bison) cows would be reduced over a period of 5 yr after one treatment with 3000 mg gonadotropin-releasing hormone immunocontraceptive (GonaCon) compared to a similar group of naturally infected B. abortus–positive bison cows not treated with GonaCon. In each of the 5 yr, GonaCon-treated cows produced fewer offspring in relation to number of cows than the nontreated cows. Fisher's Exact test comparing offspring produced during the first reproductive season showed a significant difference between the two groups (P=0.0028). Differences in number of calves produced in GonaCon-treated and control groups were also noted in remaining years, but statistics were not applied because of data constraints. These data indicate that one treatment with GonaCon in brucellosis-seropositive female bison reduced pregnancies over five reproductive years. Thus, immunocontraception could potentially be used to manage brucellosis in affected herds. [ABSTRACT FROM AUTHOR]

The physiological mechanisms controlling ovarian follicular growth and ovulation involve a complex exchange of systemic signals and a localized exchange of molecules between the oocyte and surrounding somatic cells. It has been demonstrated that the oocyte itself plays an essential role in regulating these processes by secreting two key regulatory proteins: bone morphogenetic protein-15 (BMP15) and growth and differentiation factor-9 (GDF9). Natural mutations in their expression and vaccination against these growth factors have been shown to cause sterility in sheep. The aim of this 3-year study was to determine the effect of vaccination against GDF9 and BMP15 on fertility in female white-tailed deer. Does were randomly assigned to two groups (n = 10/group). Each doe received a primary vaccination followed by a booster 47 days later. After the first year, a subset of animals (n = 4-5/group) received an additional booster vaccination. Blood samples were collected at regular intervals to determine antibody titers and progesterone concentrations. Early pregnancy was assessed by ultrasound, and fawning was subsequently monitored. For the BMP15 group, over the 3 years 80%, 100%, and 75% of does fawned with fawning rates of 2.4, 3.5, and 3.3 fawns/doe, respectively. For the GDF9 group, 80%, 25%, and 25% of does fawned with fawning rates of 2.6, 1, and 2 fawns/doe, respectively. The fawning rate of untreated animals in the herd was 1.8 fawns/doe. Although all animals in the BMP15 group had high antibody titers, they were not made infertile, and they became more fecund. Most animals in the GDF9 group had high antibody titers, but fecundity was not affected the first year; however, they were made infertile in Years 2 and 3. Results from this study demonstrate that vaccination against GDF9 has potential to control fertility in deer. Further research will be required to determine the appropriate timing for administering the vaccine and the longevity of effect.

Resident populations of two exotic deer species, fallow deer and axis deer, are having adverse impacts on their habitat and on native plant and animal communities at Point Reyes National Seashore (PRNS) in California. These non-native cervids were released intentionally for recreational hunting on the property now known as PRNS during the period 1942-1954. Approximately 860 fallow deer and 250 axis deer now inhabit PRNS. Under an approved non-native deer management plan, fallow and axis deer populations will be removed from PRNS by 2021 via culling of animals by sharpshooting and by treatment of some of the female fallow deer with GonaCon™ Immunocontraceptive Vaccine. During July-August 2007, 69 fallow does were captured, equipped with numbered ear tags and radiotelemetry collars, and injected with GonaCon™ vaccine before being released. Control animals include 10 does that were captured, marked, and given “sham” injections during July-August 2007, and 19 does that were captured and marked (but not injected) during 2005. Reproductive activity, as indicated by lactation and fecal concentrations of progesterone among the GonaCon™-treated and control does, will be monitored and compared for two years, and will be used to determine the efficacy of GonaCon™ as a cervid contraceptive agent. Traditional methods of population control, such as regulated harvest by licensed hunters, often are impractical or illegal in settings such as national and state parks, and the use of firearms may be prohibited in some urban and suburban environments. The development of safe and effective wildlife contraceptives such as GonaCon™ is needed to control locally overabundant populations in situations where traditional management tools cannot be employed.

The term “vaccine” has traditionally been associated with establishing immunity (antibodies) to a disease. This immunity is usually developed following administration of killed microorganisms. Disease vaccines typically require 1 to 3 injections, depending on the antigen design and efficacy of the vaccine. The effectiveness of the disease vaccine depends on the immune response developed by the host following exposure to the disease organism. The immunocontraceptive vaccine GonaCon™ is designed to produce immunity to the “self” hormone (GnRH), which is essential to reproductive activity in the mammal. Antibodies to GnRH reduce its biological activity resulting in infertility of both sexes. GonaCon™’s effectiveness as a single-injection immunocontraceptive wildlife vaccine depends on 4 factors. The first is the use of a large foreign mollusk protein in the GnRH conjugate. Second is the design of mollusk/GnRH protein conjugate that presents the GnRH antigen in a repetitious fashion. This design mimics the “danger signal” found in bacterial pathogens to which the animal has been previously exposed. Third is the addition to the vaccine of micrograms of Mycobacterium avium, which is ubiquitous in the environment and activates memory cells. The fourth factor is use of a water-in-oil emulsion, which provides a depot at the injection site, allowing a slow release of the vaccine. With this formulation, the vaccine is presented to the body as a “chronic infection”, even though it is not infectious. The granuloma that normally develops at the injection site plays a prime role in the host’s defense against this “chronic infection”. A WHO report on the use of the alum adjuvant in human vaccines states that “development of a small granuloma is inevitable with vaccines adjuvanted with aluminum, and is to be considered necessary to the efficacy of the adjuvant.” Researching GonaCon™ for use in companion animals, NWRC has looked at many different adjuvants intended to reduce the injection site reaction while at the same time retaining an effective vaccine. This paper reports on the role of the adjuvant and the injection site on the effectiveness of the vaccine.

GonaConTM is a single-shot immunocontraceptive vaccine that targets the reproductive hormone gonadotropin releasing hormone (GnRH). The GnRH peptide used in the vaccine is secreted by the hypothalamus of the brain and is specifically known as luteinizing hormone releasing hormone. This peptide stimulates the synthesis and secretion of luteinizing hormone and follicle stimulating hormone by the anterior pituitary gland. These hormones in turn stimulate hormone and gamete production by the ovary. In earlier studies with deer, we showed that antibodies produced in response to a single shot of GonaCon inactivated endogenous GnRH and greatly reduced fertility, reproductive steroids, and associated behaviors for at least 2 years. In the present study, we report on contraceptive efficacy and behavioral observations up to 6 years after female white-tailed deer were given a single shot of one of several formulations of GonaCon. We compared the standard GonaCon made by conjugating the GNRH peptide to keyhole limpet hemocyanin (GonaCon-KLH) to one with the GnRH peptide conjugated to a blue mollusk protein (GonaCon-Blue) and to a 2-shot regimen with GonaCon-KLH. All GonaCon preparations were made into an emulsion with AdjuVacTM and administered to 5 mature female deer per treatment. The results showed that the GonaCon-Blue preparation significantly out-performed the other single-shot vaccines, as well as the 2-shot regimen of GonaCon-KLH, with efficacy of 80-100% for each of the 5 years in the study. Interestingly, expression of estrous behavior was minimal in Years 1-2 following treatment for all groups, but expression of estrus increased in later years of the study, even though does remained infertile. This expression of estrus and fertility was reversed with follicle stimulating hormone releasing hormone (FSH-RH) peptide conjugated to a mollusk protein and mixed as an emulsion with AdjuVac. This suggests that does possess an FSH-RH peptide, secreted by the hypothalamus, which modulates follicle development and resulting estrogen production and reproductive behavior.

Recently, wildlife contraception became a reality with the registration of OvoControl for geese and pigeons. A data submission to the Environmental Protection Agency for the registration of GonaCon™ for white-tailed deer is forthcoming. The question that is now facing wildlife managers is if, and how, to implement contraception as part of an overall management plan. Population models offer a method of predicting the long-term efficacy of management actions without investing time and money in expensive field studies. Black-tailed prairie dogs were used as a target species for the purposes of these models. Four different management options were modeled for a 100-year period including no control, lethal control only, fertility control only, or a combination of lethal and fertility control. Yearly culling resulted in a more rapid rate of population decline than yearly contraception. Culled populations (50-90% culling) went extinct more quickly than populations contracepted at the same rate. Populations could be stabilized at their current size with 12.79% yearly culling or 33.25 % yearly contraception. Populations also remained relatively stable over 100 years when 50% of the population was culled initially, followed by 85.8% contraception once every 3 years. These models will help provide a scientific basis for further discussion on the usefulness of wildlife contraceptives, and will help highlight the areas that need further research.

As part of the Reproductive Control Methods Project, the USDA National Wildlife Research Center (NWRC) has developed multiple non-lethal contraceptive tools to control population of over-abundant wildlife species. Working in conjunction with Dr. G. P. Talwar of the Talwar Research Institute in India, scientists at NWRC have shown that a recombinant form of GnRH peptide has successfully contracepted swine. Feral swine not only pose a significant agricultural issue due to over-population; they act as a reservoir for Brucella suis, a threat to domestic livestock and humans. The Brucella abortus RB51 (Rough Brucella) vaccine, developed for bovine brucellosis and licensed by the USDA Animal Plant Health Inspection Service, has shown protection for some swine and is also effective against Brucella suis infection and other antigens. There is currently no approved vaccine for swine brucellosis (feral or domestic) in the United States. Past studies performed at The Ohio State University show that Brucella suis vaccination appears to protect against abortion and colonization in pigs after a virulent challenge. The Talwar recombinant peptide consists of 5 LHRH peptides interspersed with 4 universally immunogenic “promiscuous” T-cell epitopes of diverse genetic background. By transforming the Brucella suis strain with the Talwar recombinant LHRH plasmid, the bacteria will produce both its own host proteins, and the LHRH protein. A systemic immune response should then be generated to the Brucella suis proteins being produced, allowing for vaccination to Brucella suis. In addition, an immune response would be generated to the LHRH proteins resulting in antibody production and immunocontraception. A broad range of applications can be proposed utilizing the recombinant LHRH, such as other dual vaccines and scale-up production of a low-cost single-injection LHRH vaccine.

Greater demand for non-lethal means of alleviating human-wildlife conflict has led to an interest in contraception as a wildlife management tool. The development of a single-injection Gonadotropin-Releasing Hormone (GnRH) contraceptive vaccine by the USDA National Wildlife Research Center reduces logistical limitations and the cost of using a vaccine that requires 2 injections. This study assesses the efficacy of different GnRH-KLH (keyhole limpet hemocyanin) vaccine designs. Forty-two captive female black-tailed deer were divided into 3 groups. A control group was injected with saline solution, and 2 treated groups were given either GonaCon™, a GnRH vaccine paired with AdjuVac™ (an adjuvant containing 175 µg of killed Mycobacterium avium), or GnRH vaccine without AdjuVac™ (instead substituting DEAE-dextran/oil (DD) as the adjuvant). Pregnancy rates in deer treated with GonaCon™ were significantly reduced as compared to saline controls (P = 0.006). There was no significant difference between GnRH-DD compared to saline (P = 0.297). Significant difference was found between GonaCon™ and GnRH-DD (P = 0.055). Vaccinated does that remained fertile received booster injections according to treatment group and were administered either GonaCon™ containing 87 µg M. avium or GnRH-KLH conjugate bound to DEAE-dextran. Deer that received booster injections regardless of the adjuvant were 100% contracepted for 1 year. Six out of 10 deer that received a prime injection of GonaCon™ remained 100% contracepted for 3 years, suggesting that the killed M. avium in the adjuvant is essential for the success of GonaCon™ as a single-injection GnRH vaccine.

Despite the fact that many wildlife species have become overabundant both in North America and other parts of the world, the public is increasingly unwilling to manage wildlife populations with traditional techniques such as trapping or lethal methods. A growing segment of the public is urging the use of contraceptives to reduce populations of overabundant free-ranging wildlife. In spite of public pressure, the development and use of wildlife fertility control techniques has been slow to occur, partially because of the difficulty in developing efficient, cost-effective methods, and partially because of misconceptions about these potential techniques. The regulatory authority for contraceptives has recently been moved from the Food and Drug Administration (FDA) to the Environmental Protection Agency (EPA); the extensive EPA registration process is both rigorous and costly. Only one wildlife contraceptive is currently registered and available: the National Wildlife Research Center (NWRC) worked to develop a product for reducing the hatchability of Canada goose eggs in cooperation with Innolytics, LLC, who holds the registration for OvoControl® G. Development is continuing for additional experimental products. Another product developed by the NWRC, the single-shot GonaCon™ Immunocontraceptive Vaccine is poised to begin the registration process. A third product, DiazaCon™, will be soon tested for field efficacy and should begin the registration process within the year. No single wildlife contraceptive technique would be applicable for use in all wildlife species and for all management situations for a particular species. Differences in animal physiology and behavior, as well as differences in the ecology of the damage, affect which contraceptives will be most effective. Therefore, contraceptives with different modes of action will need to be developed for different species and uses. Wildlife contraceptives will not replace other management tools and will probably have a limited use, primarily in urban/suburban areas. In most species, wildlife contraceptives will not rapidly reduce populations. Populations of short-lived species such as rodents could be rapidly reduced with contraceptives; however, in long-lived species such as deer and horses, it would take years to reduce populations with fertility control alone, and damage caused by those species will continue to occur. This manuscript will discuss what contraceptive techniques are being developed by the USDA Wildlife Services NWRC, and when, where, and for what species they may be applicable.

Controlling fertility of feral horses through the use of long-acting contraceptives or sterilization approaches has been championed as a reasonable and humane solution for addressing overpopulation problems in several western states. However, methods to accomplish long-term contraceptive efficacy of horses following a single treatment have been lacking. In fall 2002 and spring 2003, we initiated a study to compare the long-term efficacy of a single-shot contraceptive vaccine directed at gonadotropin releasing hormone (GonaCon™) to that of a single-shot vaccine directed at the zona pellucida (SpayVac) and to the use of intrauterine contraceptive devices (IUD). Both vaccines were administered with AdjuVac™, an adjuvant developed at the National Wildlife Research Center. The objectives of the study were to determine: 1) 3-year efficacy for preventing pregnancy, 2) whether the contraceptive effects are reversible, and 3) whether there are contraindications. The Nevada Department of Agriculture provided the feral mares, which were maintained at the Nevada State Penitentiary, Carson City, facility. Mares were dewormed and given health vaccinations annually. Eight untreated control mares were compared to 12 mares treated with SpayVac, 16 mares treated with GonaCon™, and 15 mares treated with copper-containing IUDs. Only 25% (2/8) of the control mares were not pregnant or infertile in the first year. All mares in the SpayVac group were infertile, and 94% (15/16) were infertile in the GonaCon™ group during the first breeding season. In Year 2, 80% (10/12) of the SpayVac-treated mares and 60% (9/15) of the GonaCon™-treated mares were infertile. In Year 3, 80% of the SpayVac mares and 53% (8/15) of the GonaCon™-treated mares were infertile. For IUD-treated mares, 80% (12/15) were infertile after Year 1, but only 29% (4/14) and 14% (2/14) were infertile after Years 2 and 3, respectively. For IUD mares that were infertile, it was possible to visualize the IUD by ultrasonography, leading us to conclude that mares that became pregnant had lost their IUDs. For mares given SpayVac, uterine edema was commonly observed. In Years 2 and 3, antibody titers for SpayVac were progressively lower compared to titers observed in Year 1.

High deer densities increase vehicle collisions, damage agricultural crops, and amplify the spread of zoonotic and animal diseases, intensifying human-deer conflict. In addition, deer impact on forest vegetation can influence the distribution and abundance of other wildlife species. Greater demand for non-lethal means of animal damage control has led to an interest in contraception as a wildlife management tool. The development of a single-injection Gonadotropin-Releasing Hormone (GnRH) contraceptive vaccine by NWRC reduces logistical limitations and cost of using immunocontraception as compared to a vaccine that requires two injections. This study assessed the efficacy of two different GnRH-KLH (keyhole limpet hemocyanin) vaccine designs in a single-injection study, to determine if Mycobacterium avium bacterium in the adjuvant is necessary for the success of a single-injection contraceptive vaccine. Forty-two captive female black-tailed deer were divided into 3 groups. Control deer were injected with saline solution, one treatment group received GonaCon™ (a GnRH-KLH vaccine paired with AdjuVac™ adjuvant that contains a small quantity of killed M. avium bacterium), and the second treatment group received GnRH-KLH vaccine with DEAE-Dextran/oil as the adjuvant. Contraceptive success was evaluated by monitoring progesterone, pregnancy specific protein, antibodies to GnRH-KLH conjugate and to Johne’s bacterium (M. avium), and actual pregnancy rates. Pregnancy rates were significantly different based on treatment (X² = 9.389; df = 2; P = 0.009). Pregnancy rates in deer treated with GonaCon™ were significantly reduced as compared to saline controls (P = 0.006), but there was no significant difference between GnRH-DD compared to saline (P = 0.297). Significant difference was found between GonaCon™ and GnRH-DD (P = 0.055). Results suggest that M. avium in the AdjuVac™ adjuvant is essential for the success of the single-injection GnRH vaccine GonaCon™. The development of a single-injection vaccine will increase the practicality and lower the cost of using immunocontraception as a tool to control deer populations.

GonaCon™ Immunocontraceptive Vaccine targets the reproductive hormone gonadotropin releasing hormone (GnRH) secreted by the hypothalamus of the brain. Antibodies produced in response to the vaccine inactivate endogenous GnRH, which in turn eliminates stimulation of the pituitary gland and gonads in males or females. The resulting “immunocastration” renders animals unable to produce reproductive steroids or gametes. In previous studies, we demonstrated that GonaCon™ was effective in impairing fertility for up to 3 years in female deer without apparent side effects. However, detailed post mortem evaluations were not done. To better understand the entire physiological response of deer to GonCon™ and to establish if contraindications were associated with its use, we undertook the present study. To evaluate toxicity and safety, 7 does were given the standard single injection GnRH-KLH vaccine dose (1000 µg) delivered IM in 1 ml using AdjuVac™ adjuvant and compared to 6 does given a single control saline IM injection and 6 does given 3 injections of GonaCon™ at 2-week intervals per dose. The study was conducted for 20 weeks. Does were blocked by weight and randomly assigned within blocks to treatment groups. Blood samples were drawn immediately prior to vaccination and at 5, 10, 15, and 20 weeks post immunization. Blood was assayed for LH, testosterone and progesterone, and anti-GnRH titers, as well as hematology and blood chemistry. At each sampling period, the general health of the doe was observed and the injection site was inspected for the formation of abscesses or other tissue reactions. At Week 20, all deer were euthanized and evaluated at necropsy by veterinary pathologists and samples of lymph nodes, reproductive organs, lung, liver, heart, kidney, spleen, and brain were taken for histology. Aside from granulomata formation at the injection site, there were no significant contraindications or toxic effects associated with GonaCon™.

The use of poisons for coyote control is controversial because of public opposition to lethal control of pest animals and the perceived environmental risks of pesticide use. The development of immunocontraception for population control of coyotes could result in a more acceptable alternative to poisons. Immunocontraception using porcine zona pellucida (PZP) would allow normal estrus in the female and therefore normal male-female pair-bonding. Coyotes are mon-estrus, therefore PZP contraception during the breeding season of February and March could provide year-round protection. This paper reviews 9 years of research on PZP immunocontraception, starting from a multi-shot PZP vaccine using Freund’s adjuvant, to the development and testing of two single-shot preparations combined with a newly developed adjuvant (AdjuVac™). We provide insights into the false assumption that one contraceptive vaccine fits all species and situations.

GonaCon™ is a gonadotropin releasing hormone (GnRH) contraceptive vaccine developed at the USDA National Wildlife Research Center (NWRC) that contains keyhole limpet hemocyanin (KLH) coupled to GnRH. The vaccine is administered intramuscularly in an emulsion with the NWRC adjuvant, AdjuVac™. This first-generation vaccine, developed in 1998, has been very effective in contracepting every species tested. However, because of the high cost of KLH, NWRC has developed a second generation GnRH vaccine, replacing KLH with a less expensive mollusk protein. This second generation GnRH vaccine, called GonaCon-Blue™, is currently being tested in several species and has proven to be as, or more effective than the original GonaCon™. Scientists with the Reproductive Control Methods Project at the NWRC are also testing a recombinant GnRH antigen developed by Dr. Talwar of the Talwar Research Institute, India. The recombinant antigen was produced from plasmid gene expression grown in and extracted from E. coli. The antigen is combined with the NWRC AdjuVac™ to form an emulsion similar to the GonaCon™ preparation. The recombinant vaccine has been shown to be effective as a single or dual injection for contraception of adult female pigs in a short-term study at the Swine Research Facility at Penn State University. Although the long term effectiveness of the recombinant vaccine remains to be established, this small molecule of approximately 14,000 MW is of considerable interest because it may be effective in oral or transcutaneous applications. It could also be scaled-up for large field applications.

Locally overabundant deer herds, particularly those inhabiting fenced or other enclosed areas in urban or suburban settings, are presenting serious problems for wildlife managers, landowners, and the general public. Traditional methods of population control, such as regulated harvest by licensed hunters, often are impractical or illegal in such settings. The development of safe and effective wildlife contraceptives is needed to control locally overabundant populations in situations where traditional management tools cannot be employed. During July 2004, we initiated a field study of GonaCon™ Immunocontraceptive Vaccine, developed by research scientists at the National Wildlife Research Center in Fort Collins, Colorado. This vaccine had previously been tested successfully as a contraceptive in captive animals including white-tailed deer, feral and domestic swine, and wild horses. The two-year field study was prompted by the need to manage an enclosed, overabundant population of white-tailed deer that had caused considerable ecological damage to a 662-acre, federally-owned, forested site in Silver Spring, Maryland. The U.S. General Services Administration, which manages the property, conducted an environmental assessment, which concluded that sharpshooting followed by immunocontraception would be the most appropriate deer management strategy. After 214 deer were removed from the site by sharpshooters, we set up and tested an automated radio telemetry system for tracking deer and monitoring their mortality. Twenty-eight does were then captured, equipped with ear tags and radio telemetry collars, and injected with GonaCon™ vaccine. Fifteen additional does were captured, marked, and released without vaccination as untreated control animals. Reproductive behavior and fawn production by the vaccinated and unvaccinated does will be monitored and compared for two years, and will be used to determine the efficacy of GonaCon™ as a wildlife contraceptive agent. Data from this study will be used to support EPA registration of GonaCon™ as a wildlife contraceptive agent.

Avian contraception is a nonlethal management tool that can be utilized in conjunction with other management techniques to help manage bird populations causing damage. Because management situations vary with respect to the type of damage, species involved, location, and nontarget hazards, it is necessary to develop multiple contraceptive tools to allow management flexibility. DiazaCon™ and nicarbazin have already been developed at the National Wildlife Research Center as avian contraceptives. Although both of these are promising contraceptive agents, more are needed for a wider variety of situations. Current research is focusing on other cholesterol inhibitors, inhibitors of the P450 side chain cleavage enzyme, and aromatase inhibitors. Because cholesterol is needed for steroid reproductive hormone production, inhibition of cholesterol impairs reproduction by preventing the formation of the necessary hormones. The P450 side chain cleavage enzyme is needed to convert cholesterol to pregnenolone, the precursor to progesterone and testosterone. Progesterone is needed for egg formation, ovulation, and oviposition, and testosterone is needed for sperm production. Aromatase is needed to convert testosterone to estradiol, which is needed in females to stimulate the production of egg yolk precursors in the liver. Inhibition of either of these enzymes should result in impaired reproduction. In the future, natural plant products with contraceptive activity, such as neem seed, will also be investigated. Because development of avian contraceptives is time intensive, an efficient screening process needs to be in place. Population models can assist in choosing specific agents to test for a given species and management situation. Although contraception is unlikely to be useful as a stand-alone tool, it can be included in integrated management plans.

Overpopulation of feral horses in several western states is an unquestioned problem. Current management strategies of removal and adoption are expensive, logistically challenging, and ineffective as a means of population control. We are testing three long-acting contraceptive approaches on feral Nevada mares. Modified reversible immunocontraceptive vaccines for gonadotropin releasing hormone (GnRH) and porcine zona pellucida (PZP) (SpayVac), and intrauterine contraceptive devices (IUDs), are being evaluated to determine: 1) their safety and efficacy for preventing pregnancy for multiple years, 2) whether the effects are reversible, and 3) whether there are notable contraindications. Preliminary data after 1 year suggest that IUD- and PZP-treated mares continue to exhibit breeding and estrus, while GnRH-treated mares are less likely to cycle. All mares in the GnRH and PZP treatments were infertile for the breeding season. Eighty percent of the IUD-treated mares were infertile; those mares that became pregnant likely failed to retain the IUD. A notable contraindication was that uterine edema normally observed in mares in the follicular phase of the estrous cycle was commonly observed in PZP-treated mares. Because administration of each contraceptive approach is different, and each has different effects and expected duration, one approach or a combination of approaches may be best suited for specific field applications. Subsequent years of this study should establish the efficacy and safety of one or more long-acting contraceptive approaches for feral horse population control.

Populations of wildlife, such as California ground squirrels, can grow to the extent that they come in conflict with humans. Contraception is a method of population management under investigation that may be useful in situations where neither leaving the animals uncontrolled nor lethal control are apropos. In this study, we tested the use of a single-injection gonadotropin releasing hormone (GnRH) immunocontraceptive vaccine in urban California ground squirrels. We monitored the effects of treatment for two breeding seasons. Immunization reduced the proportion of females lactating by 91% the first year and 96% in the second year. Testicular development was inhibited 35% the first year and 89% the second year. There is a delay of several months from the time of injection to inhibition of testes development. Reduction in the number of juveniles born per adult as determined by a visual count index was 9% the first year and 66% the second year. This study shows that the single-shot GnRH vaccine is over 90% effective for at least 1.5 years and requires several months after immunization for contraceptive effect. Because the immunization requires injection, it is labor intensive, but it is much more practical than treatments requiring multiple administrations to the same animal. GnRH immunocontraception may be a useful tool in rodent population management in certain circumstances.

As part of the program to develop contraceptive tools to control populations of over-abundant wildlife species, the NWRC has developed a single-injection gonadotropin-releasing hormone (GnRH) immunocontraceptive vaccine, GonaCon™. GonaCon™ has been tested and shown to provide contraceptive effects lasting 1-3 years in many pest species including white-tailed deer, domestic and feral pigs, bison, wild horses, cats, dogs, and California ground squirrels. GonaCon™ contains a GnRH peptide conjugated to keyhole limpet hemocyanin combined with AdjuVac™, an adjuvant also developed at the USDA National Wildlife Research Center. Immunization against GnRH prevents the circulating GnRH from stimulating the release of pituitary luteinizing hormone and follicle-stimulating hormone. This process of immuno‑neutralization of GnRH effects a temporary non‑surgical castration in both males and females. Contraceptive and behavioral effects of GonaCon™ are discussed for a variety of species.

A growing interest in nonlethal methods for population control of nuisance or damaging species of wildlife has fostered research in reducing fertility of these overabundant wildlife species. Fertility may be reduced by interfering with the fertilization of the egg (contraception) or interfering with the implantation or development of the fertilized egg (contragestion). Research using injectable porcine zona pellucida (PZP) and gonadotropin releasing hormone (GnRH) vaccines has demonstrated that several mammalian species can be contracepted, reducing fertility for several years without revaccination. However, because vaccines currently require delivery by syringe or bio-bullet, there is a need for infertility agents that can be delivered orally. Researchers are therefore considering materials that have resulted in reduced reproductive rates in the agricultural industry. Because of the cost of getting new technology approved by the FDA, materials already approved for other purposes that can be redirected for use in wildlife infertility may have a better chance of getting approved as wildlife infertility agents. Two compounds used in the broiler chicken industry have been found to reduce hatchability if given to the layer. Due to the rapid increase of Canada geese in our parks, research is ongoing with these two compounds to reduce hatchability in the Canada goose egg. Research is also underway to test a cholesterol mimic that competes with cholesterol as the parent compound for steroid synthesis. This compound could reduce fertility in both mammalian and avian species and is currently being tested in rodents. Natural plant materials such as phytoestrogens and ergot derivatives that result in reproductive losses in domestic animals should be also explored as reproductive inhibitors in overabundant species of wildlife.

Fertility control in wildlife is emerging as a potential management tool. Published research on feral horses, deer, rodents, and rabbits suggest an effective agent producing reversible infertility in these species could be developed. Furthermore, anecdotal reports suggest that infertility can be induced in a greater array of species. In this paper, the authors review methods of fertility control being studied for application in wildlife and focus on their studies designed to evaluate the effectiveness of fertility control agents in coyotes (Canis latrans). Immunocontraception using porcine zona pellucida (PZP) is currently the most promising method of fertility control in coyotes the authors have studied. This is consistent with results from other species. However, the vital question of whether any fertility control agent can reduce livestock losses due to coyote predation will require more research.