Effects of the Immunocontraceptive Gonacon on Pregnancy in Brucella-Seropositive American bison (Bison bison).

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 µg 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.

Major locus on ECA18 influences effectiveness of GonaCon vaccine in feral horses.

Contraceptive vaccines are used to reduce birth rates in wild and feral animal populations. While the immunocontraceptive GonaCon-Equine has proven effective in reducing fertility among female feral horses, there is individual variation in the duration of infertility following treatment. To identify genetic factors influencing the effectiveness of GonaCon-Equine, we conducted a genome-wide association study of 88 mares from a feral population genotyped using the Illumina GGP Equine 70k SNP array. Contraceptive treatment schedules and long-term foaling rates have been recorded for each individual. We used mixed linear models to control for relatedness among mares. We found a significant association (p < 5 ×10-8) with a locus on equine chromosome 18. The most likely candidate genes in this region are STAT1 and STAT4, which are both involved in immune system function. Variation in STAT function could affect the immune response to the vaccine, leading to variation in contraceptive efficacy. Additional SNPs reaching a less stringent threshold of significance (p < 5 ×10-6) were located on other chromosomes near known immune system genes, supporting the hypothesis that variation in immunocontraceptive efficacy can be attributed to genetic variation in immune response rather than fertility genes.

Short Term Safety, Immunogenicity, and Reproductive Effects of Combined Vaccination With Anti-GnRH (Gonacon) and Rabies Vaccines in Female Feral Cats.

Overpopulation of free-roaming cats is a major problem leading to negative impacts on animal health and welfare, public nuisance, transmission of zoonotic diseases, and well-documented harm to wildlife. Surgical sterilization had failed to provide a practical solution to free-roaming cats' overpopulation under field conditions; therefore, efficient and safe non-surgical immunocontraception methods are aspired. Rabies is a deadly virus that may infect people and animals. However, the safety and efficacy of combined vaccination with anti-GnRH and rabies vaccines in feral cats, which often suffer from disrupted health conditions and experienced high stress level, has never been studied. Therefore, our objective was to examine the short-term safety and efficacy of anti-GnRH vaccine (Gonacon), in combination with rabies vaccine in female feral cats. Mature feral female cats were captured and divided into the following groups: (I) GonaconX1-Rabies: queens vaccinated with both Gonacon and rabies (n = 5); (II) GonaconX2-Rabies: queens vaccinated twice with Gonacon (3 weeks apart) and with Rabies (n = 4); (III) OVx-Rabies: queens ovariohysterectomized and vaccinated with rabies (n = 4); (IV) Intact-Rabies: queens vaccinated against rabies and remained intact (n = 3). Comprehensive veterinary examinations and blood tests were performed every 2 weeks for 14 weeks. Data were analyzed by Repeated-Measures-ANOVA or Fisher-Exact-Test. There were neither systemic nor local adverse reactions at the vaccination sites. Blood count (PCV, TS, RBC, HGB, HCT, WBC) and chemistry (Total protein, Total globulin, Albumin, Urea, Creatinine, Creatine kinase, Bilirubin, GGT, ALT, AST) analyses revealed no differences among groups. There were no differences in serum rabies antibodies titers among groups, and queens kept a protective titer (>0.5 IU/mL) starting at 2-4 weeks after vaccination. Anti-GnRH antibodies were detected in all Gonacon-vaccinated queens, excluding one queen (GonaconX2-Rabies group). Anti-müllerian hormone serum concentrations reduced significantly after ovariohysterectomy, as well as gradually following vaccination with Gonacon, but it remained high in intact queens. Evaluation of vaginal cytology and ovarian histology suggested that reproductive cyclicity was suppressed in Gonacon-vaccinated queens. Our results support the conclusion that in the short term, the combined vaccination with Gonacon and rabies is safe and effective in female feral cats. However, further long-term studies are warranted to test this immunologic regimen in feral cats.

Field-testing a single-dose immunocontraceptive in free-ranging male capybara (Hydrochoerus hydrochaeris): Evaluation of effects on reproductive physiology, secondary sexual characteristics, and agonistic behavior.

Controlling wildlife populations to mitigate human-wildlife conflicts and the spread of zoonotic diseases is an ever-growing necessity. The objective of this study was to evaluate a single-dose anti-gonadotropin-releasing hormone vaccine (GonaCon, USDA/NWRC, Fort Collins, CO, USA) as a non-lethal alternative for population control in free-ranging, synanthropic male capybara. In addition to infertility efficacy of this treatment, potential effects on the alpha male's secondary sexual characteristics and agonist behavior need to be assessed because any alterations in these factors could lead to population management failure. The treatment group (n = 3) received 1 mL of the anti-GnRH vaccine, intramuscularly, and the control group (n = 2) a 1 mL sham vaccine. Reproductive behavior and social group dynamics were monitored for 30 days prior to inoculation (June 2017) with continuous observations occurring during the study period. Antifertility effects were assessed by conducting exams of testicular morphology, semen characteristics, and histological analysis (after 270 days via hemi-gonadectomy). Compared to the control group, the testicles of the treated males had severe atrophy (P <  0.05), oligozoospermia and greater numbers of sperm cells in a static developmental phase. Courtship and agonistic alpha male behavior were not altered, and the group's social integrity was maintained. Results indicate there was 100% infertility in capybara males, observed throughout the study period of 18 months, and equally important, the male's alpha characteristics were not affected by the treatment, which is imperative for successful capybara population control efforts.

Brazilian spotted fever prevention through a nonlethal capybara population control strategy

Abstract INTRODUCTION: Brazilian spotted fever (BSF), a lethal tick-borne Rickettsioses (2000 - 2018 >600 human deaths) involving synanthropic capybara as host. METHODS: We introduced an alternative to mitigate human-capybara conflicts and epidemiologic concerns of BSF. Complex aspects like transmission dynamics, risk areas, host mobility, and birth rate control, were considered to develop a prevention strategy using an anti-GnRH vaccine. RESULTS: The propositioned immunocontraceptive potentially remove and prevent the spread of BSF from endemic areas. CONCLUSIONS: We propose the anti-GnRH vaccine as a BSF prevention strategy based on these favorable results.

Use of a GnRH vaccine, GonaCon, for prevention and treatment of adrenocortical disease (ACD) in domestic ferrets.

Adrenocortical disease (ACD) is a common problem in surgically sterilized, middle-aged to old ferrets (Mustela putorius furo). The adrenal tissues of these ferrets develop hyperplasia, adenomas, or adenocarcinomas, which produce steroid hormones including estradiol, 17-hydroxyprogesterone, and androstenedione. Major clinical signs attributable to overproduction of these hormones are alopecia (hair loss) in both sexes and a swollen vulva in females. Pruritus, muscle atrophy, hind limb weakness, and sexual activity or aggression are also observed in both sexes. Males can develop prostatic cysts, prostatitis, and urethral obstruction. ACD is thought to be linked to continuous and increased LH secretion, due to lack of gonadal hormone feedback in neutered ferrets. This continuous elevated LH acts on adrenal cortex LH receptors, resulting in adrenal hyperplasia or adrenal tumor. This study investigated whether the immunocontraceptive vaccine GonaCon, a GnRH vaccine developed to reduce the fertility of wildlife species and the spread of disease, could prevent or delay onset of ACD and treat alopecia in ferrets with existing ACD. Results showed that GonaCon provided relief from ACD by causing production of antibodies to GnRH, probably suppressing production and/or release of LH. Treatment caused many ACD symptoms to disappear, allowing the ferrets to return to a normal life. The study also found that the probability of developing ACD was significantly reduced in ferrets treated with GonaCon when young (1-3 years old) compared to untreated control animals. GonaCon caused injection site reaction in some animals when administered as an intramuscular injection but caused few side effects when administered subcutaneously. Both intramuscular and subcutaneous vaccination resulted in similar levels of GnRH antibody titers. Subcutaneous vaccination with GonaCon is thus recommended to prevent the onset of ACD and as a possible treatment for ACD-signs in domestic ferrets.

Concomitant administration of GonaCon™ and rabies vaccine in female dogs (Canis familiaris) in Mexico.

Mexico serves as a global model for advances in rabies prevention and control in dogs. The Mexican Ministry of Health (MMH) annual application of approximately 16 million doses of parenteral rabies vaccine has resulted in significant reductions in canine rabies during the past 20 years. One collateral parameter of rabies programs is dog population management. Enhanced public awareness is critical to reinforce responsible pet ownership. Surgical spaying and neutering remain important to prevent reproduction, but are impractical for achieving dog population management goals. GonaCon™, an anti-gonadotropin releasing hormone (GnRH) vaccine, was initially tested in captive female dogs on the Navajo Nation, 2008. The MMH led this international collaborative study on an improved formulation of GonaCon™ in captive dogs with local representatives in Hidalgo, Mexico in 2011. This study contained 20 bitches assigned to Group A (6 control), Group B (7 GonaCon™), and Group C (7 GonaCon™ and rabies vaccine). Vaccines were delivered IM. Animals were placed under observation and evaluated during the 61-day trial. Clinically, all dogs behaved normally. No limping or prostration was observed, in spite of minor muscle atrophy post-mortem in the left hind leg of dogs that received GonaCon™. Two dogs that began the study pregnant give birth to healthy pups. Dogs that received a GonaCon™ injection had macro and microscopic lesions consistent with prior findings, but the adverse injection effects were less frequent and lower in intensity. Both vaccines were immunogenic based on significant increases in rabies virus neutralizing antibodies and anti-GnRH antibodies in treatment Groups B and C. Simultaneous administration of GonaCon™ and rabies vaccine in Group C did not affect immunogenicity. Progesterone was suppressed significantly in comparison to controls. Future studies that monitor fertility through multiple breeding cycles represent a research need to determine the value of integrating this vaccine into dog rabies management.