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.

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.

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.

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.

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.

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.

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.

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.

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.

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.