Kathleen A. Fagerstone

The Single-Shot GnRH Immunocontraceptive Vaccine (GonaCon TM ) in White-Tailed Deer: Comparison of Several GnRH Preparations

Problem  An effective, single‐injection, multi‐year, GnRH contraceptive agent is needed to control reproduction in overabundant white‐tailed deer populations.

Long-term fertility control in female cats with GonaCon™, a GnRH immunocontraceptive.

The uncontrolled reproduction of free-roaming feral cats contributes to overpopulation and associated concerns regarding their welfare and impact on public health and the environment. Nonsurgical fertility control that could be administered to feral cats in the field would be a powerful tool for cat population control. The objective was to test the efficacy and duration of activity of a single-dose GnRH immunocontraceptive vaccine (GonaCon™) on the fertility of adult female laboratory cats. Vaccinated cats (n = 15) received a single injection of vaccine containing a GnRH-KLH conjugate (200 μg) emulsified in a mycobacterial and oil adjuvant on study Day 0. Sham-treated cats (n = 5) received a single injection containing all vaccine components except the GnRH-KLH conjugate. A breeding trial started on study Day 120. Vaccinated cats had a longer time to conception (median 39.7 mo) compared to sham-treated cats (4.4 mo; P < 0.001). A total of 93% of vaccinated cats remained infertile for the first year following vaccination, whereas 73, 53, and 40% were infertile for 2, 3, and 4 y, respectively. At study termination (5 y after a single GnRH vaccine was administered), four cats (27%) remained infertile. The GnRH antibody titers declined more rapidly in short-term responding cats with < 2 y of infertility (n = 4), compared to long-term responding cats that experienced fertility control for >2 y (n = 11) (P < 0.05). Non-painful but persistent late-onset granulomatous injection site masses appeared 2 y after initial vaccination in five cats. We concluded that GnRH immunocontraception is an ideal candidate for further development for feral cat control.

A review of existing and potential New World and Australasian vertebrate pesticides with a rationale for linking use patterns to registration requirements

Registration is a necessarily sophisticated evaluation process applied to vertebrate pesticide products. Although conducted to minimise any potential impacts upon public health, the environment and food production, the all-encompassing process of registration can stifle innovation. Vertebrate pesticides are rarely used to control pest animals in food crops. In contrast to agrochemicals, relatively small amounts of vertebrate pesticides are used (<0.1%), usually in solid or paste baits, and generally by discrete application methods rather than by broad-scale spray applications. We present a hierarchy or sliding scale of typical data requirements relative to application techniques, to help clarify an evolving science-based approach which focuses on requiring data to address key scientific questions while allowing waivers where additional data have minor value. Such an approach will facilitate the development and delivery of increasingly humane, species-targeted, low residue pesticides in the New World, along with the phasing out of less desirable chemicals that continue to be used due to a lack of alternatives.

Observations on the Use of GonaconTM in Captive Female elk (Cervus Elaphus)

Overabundant populations of elk (Cervus elaphus) are a significant concern in some areas of the western United States because of potential ecologic damage and spread of brucellosis to domestic livestock. Brucella abortus is transmitted among elk through direct contact with aborted fetuses, placentas and associated fluids, or postpartum discharge of infected animals. Because transmission of brucellosis is dependent on pregnancy, contraception of cows could be used for both disease and population management. The objective of this study was to evaluate the contraceptive efficacy of a gonadotropin-releasing hormone vaccine (GonaConTM) in female elk. In September 2004, cows were given a single immunization of either 1,000 μg (n=12) or 2,000 μg (n=10) of GonaConTM and compared with a group of adjuvant-treated controls (n=15). In November 2004, 2005, and 2006, cows were grouped with bulls for the breeding season. Blood samples were taken in February 2005 and March 2006 and 2007 for pregnancy testing, progesterone assays, and antibody titers. For cows given 1,000 μg GonaConTM the percentages that were infertile for 2005, 2006, and 2007 were 86%, 90%, and 100%, respectively, compared with 90%, 100%, and 100% for cows given 2,000 μg GonaConTM. Rates of infertility for control cows were 23%, 28%, and 0% (P<0.0001). The results indicated that either dose of GonaConTM prevented pregnancy of elk cows for at least 3 yr. We concluded that GonaConTM use for population management of elk warrants consideration as part of a strategy to control brucellosis.

Field test of a single-injection gonadotrophin-releasing hormone immunocontraceptive vaccine in female white-tailed deer

Thedevelopmentanduseofsafe,effectiveandpracticalwildlifecontraceptiveagentscouldreducereproduction inlocally overabundant deer populationsinsituations where traditionalmanagement toolssuch as regulated huntingcannot be employed. GonaCon Immunocontraceptive Vaccine (the commercial name for a particular gonadotrophin-releasing hormone(GnRH)-basedemulsion)wastestedinadultfemalewhite-taileddeerinafencedherdnearSilverSpring,Maryland, USA. Observations of udder condition were used to identify does that had become pregnant. Necropsy observations, histopathology and serum concentrations of anti-GnRH antibodies, luteinising hormone and progesterone were used to comparehealthandreproductivestatusoftreated(n=28)andcontrol(n=15)deer.AfterreceivingoneinjectionofGonaCon, 88% of treated deer did not become pregnant during the first year and 47% did not become pregnant during the second year aftervaccination.NoadversehealtheffectsrelatedtovaccinationwithGonaConweredetected,exceptforlocalisedinjection- site reactions in five (29%) of 17 examined, vaccinated deer. Treatment with GonaCon can be a safe and effective means of inducingtemporaryinfertilityinwildwhite-taileddeer.Ultimately,themanagementvalueofGonaConwillbedeterminedby natural-resource professionals who use it as one of many tools to manage deer populations.

Feeding of grey squirrels (Sciurus carolinensis) with the contraceptive agent DiazaCon™: effect on cholesterol, hematology, and blood chemistry

Grey squirrels (Sciurus carolinensis) are an invasive species in Britain and Italy. They have replaced native red squirrels (Sciurus vulgaris) throughout most of Britain, and cause damage to trees. Currently, lethal control is used to manage grey squirrel populations in Britain, but nonlethal methods might be more acceptable to the public. One such method is contraception with 20,25-diazacholesterol dihydrochloride (DiazaCon™). DiazaCon™ inhibits the conversion of desmosterol to cholesterol, resulting in increasing desmosterol concentrations and decreasing cholesterol concentrations. Because cholesterol is needed for the synthesis of steroid reproductive hormones, such as progesterone and testosterone, inhibition of cholesterol synthesis indirectly inhibits reproduction. Desmosterol is used as a marker of efficacy in laboratory studies with species that do not reproduce readily in captivity. Grey squirrels were gavaged with a DiazaCon™ solution for 2 days, and then fed DiazaCon™-coated peanuts for an additional 8 days at target doses of 50 and 100 mg DiazaCon™ per kg body weight. There was a significant difference in cholesterol concentrations in the treatment groups compared to the control group. Cholesterol was reduced by ≥ 40% for 2 months in both treatment groups. There were no differences among groups with respect to blood chemistry and hematology parameters, and mean values are reported. The mean overall dose of DiazaCon™ received was 29.0 ± 1.6 and 55.3 ± 4.3 mg/kg in the low (50 mg/kg) and high dose (100 mg/kg) groups, respectively. DiazaCon™ might provide an effective, acceptable alternative to lethal control.

TWENTY YEARS OF IMMUNOCONTRACEPTIVE RESEARCH: LESSONS LEARNED

Abstract:  The National Wildlife Research Center (NWRC) began immunocontraception vaccine research by testing porcine zona pellucida (PZP) on white-tailed deer (Odocoileus virginianus). Early PZP research demonstrated that PZP induced infertility; however, increased length of the rut was observed in PZP-treated deer. An alternative vaccine using a keyhole limpet hemocyanin-gonadotropin-releasing hormone (KLH-GnRH) conjugate formulated with modified Freunds adjuvant was developed at NWRC. Suppression of GnRH has reduced reproduction in both sexes but is most effective in females. This vaccine was effective in preventing contraception in female deer for several years after a prime and boost. Due to adverse side effects of Freunds adjuvant, NWRC developed a new adjuvant called AdjuVac, a mineral oil/surfactant adjuvant with the addition of Mycobacterium avium as an immunostimulant. The price of KLH prompted a search for a more economical hemocyanin carrier protein for the GnRH peptide. Blue protein, derived from the mollusk Concholepas concholepas, proved to be a successful option. Formulation improvements resulted in a vaccine that can be effective as a single injection for multiple years, now called GonaCon. GonaCon is registered with the Environmental Protection Agency (EPA) for use in white-tailed deer in urban/suburban areas and for wild horses (Equus caballus) and burros (Equus asinus). Future GonaCon applications may include reducing reproduction to manage populations of other wildlife species, such as prairie dogs (Cynomys ludovicianus) in urban areas and suppressing reproduction to reduce the spread of venereal diseases such as brucellosis. Research is being conducted to develop a GnRH vaccine used in combination with the rabies vaccine to control population growth in free-roaming dogs, with the secondary effect of managing the spread of rabies. The EPA would regulate all these uses. Research is also ongoing on a GnRH vaccine to delay the onset of adrenocortical disease in pet ferrets (Mustela putorius), a use regulated by the United States Department of Agriculture.

THE USE OF CONTRACEPTION AS A DISEASE MANAGEMENT TOOL IN WILDLIFE

Abstract:  Contraception offers potential as a tool for managing certain diseases in wildlife, most notably venereally transmitted diseases or diseases transmitted at parturition. Brucellosis is an excellent example of an infectious disease present in wild populations that could potentially be managed through immunocontraception. Previous studies in bison (Bison bison) suggest that a single injection of GonaCon™ (National Wildlife Research Center, U.S. Department of Agriculture/Animal and Plant Health Inspection Service/Wildlife Services, Fort Collins, Colorado 80521, USA) results in 3 or more yr of infertility. Ongoing studies will determine if the use of GonaCon in bison decreases shedding of Brucella abortus from infected animals and will better define the duration of infertility following a single injection

STATE-LEVEL APPROACHES TO MANAGING THE USE OF CONTRACEPTIVES IN WILDLIFE IN THE UNITED STATES

Abstract:  Several fertility control agents have recently been registered with the U.S. Environmental Protection Agency for management of wildlife or other free-ranging animals. The registration of GonaCon™ Immunocontraceptive Vaccine for use in white-tailed deer (Odocoileus virginianus) and OvoControl for use in Canada geese (Branta canadensis) and pigeons (Columba livia) has caused state wildlife and land management agencies to review their regulatory authority over the use of contraceptives in wildlife. As a result, many states are taking steps to ensure legislation or policies are current with emerging technologies. This article examines the various approaches states are taking to regulate the use of contraceptives. Regardless of the final regulatory approach, biological, social, economic, and political implications must all be discussed as this new tool is introduced into the field of wildlife management. Thoughtful consideration of all aspects of wildlife contraceptive use will lead to the development of sound, best management practices for current and future products.

ORIGINAL ARTICLE: The Single-Shot GnRH Immunocontraceptive Vaccine (GonaCon™) in White-Tailed Deer: Comparison of Several GnRH Preparations: SINGLE-SHOT GNRH IMMUNOCONTRACEPTION IN WHITE-TAILED DEER

Problem  An effective, single‐injection, multi‐year, GnRH contraceptive agent is needed to control reproduction in overabundant white‐tailed deer populations.