As human-wildlife conflicts increase worldwide, novel methods are required for mitigating these conflicts. Fertility control, based on immunocontraceptives, has emerged as an alternative option to lethal methods for managing wildlife.2. Immunocontraceptives are vaccines that generate an immune response to key components of an animal's reproductive system. Some of these vaccines target the gonadotropin-releasing hormone (GnRH) and have been used successfully as contraceptives for many wildlife species. However, the need to capture animals for treatment limits the field applications of injectable vaccines. The availability of orally delivered immunocontraceptives would increase the breadth of applications of fertility control for wildlife management.3. This study explored a new approach to developing an oral immunocontraceptive, exploiting the bioadhesive and immunologically active properties of killed Mycobacterium avium cell wall fragments (MAF). The MAF was conjugated to a GnRH recombinant protein called IMX294, used as a GnRH-specific immunogen.4. An initial trial using the MAF-IMX294 conjugate provided the first evidence that an orally delivered immunocontraceptive vaccine could generate anti-GnRH antibody titres in laboratory rats.5. Increasing the dose and frequency of vaccine administered to rats, in a second trial, enhanced the immune response, eliciting titres that reduced the proportion of females giving birth. This provided the first evidence of the contraceptive effect of an oral anti-GnRH vaccine.6. Future work is required to further increase the immunogenic effect of the oral vaccine and to establish a dosing schedule that is effective for practical field applications.
Conflicts between human interests and feral cattle in Hong Kong derive from growing numbers of free-roaming cattle. Public antipathy towards lethal population control led the local authorities to consider fertility control to reduce cattle numbers. This study assessed the potential side effects of the immunocontraceptive GonaCon on individual female cattle and established the effectiveness of GonaCon to induce infertility. We evaluated GonaCon in 34 captive cattle assigned to four groups: Control administered a sham solution; Webbed (surgically sterilized through removal of the oviducts), administered one dose of GonaCon; Webbed, administered one dose of GonaCon and a booster dose three months later, and Treated, administered one dose of GonaCon. The side effects of GonaCon were assessed by monitoring injection site, body weight, body condition, size of lymph nodes, body temperature, and feeding behaviour 1 week and 1, 3, 6, 9 and 12 months after vaccination and by haematological and biochemical variables at vaccination and three months post-vaccination. The effectiveness of GonaCon to cause infertility was monitored by quantifying anti-GnRH antibody titres and by using kits to detect cycling and pregnancy. GonaCon-treated cattle showed no injection site reaction, limping, or abnormal behaviour. No differences were observed in all physiological and welfare indicators between control and vaccinated cattle. All control cattle and 4 of the 12 cattle in the Treated group became pregnant. Cattle administered a booster dose had higher anti-GnRH antibody titres than cattle that received one dose. We concluded that GonaCon does not compromise the animals’ welfare and is effective in reducing fertility in cattle. A booster dose is likely to increase the duration of infertility. Further studies are required to assess the feasibility and costs of immunocontraception for controlling free-roaming cattle populations.
Human-wildlife conflicts are increasing worldwide. For instance, growing numbers of free-roaming feral cattle in Hong Kong are causing traffic accidents and damaging crops. Public antipathy towards lethal methods to manage wildlife has promoted research into alternative options, such as fertility control. The aims of this study were to assess the potential side effects and effectiveness of the injectable immunocontraceptive vaccine GonaCon on free-roaming feral cattle in Hong Kong. Sixty female cattle were captured and randomly assigned to treatment or control groups. Treatment animals were administered one dose of GonaCon, followed by a booster dose 3-6 months later. Control animals were administered an equivalent dose of a saline solution. The side effects of GonaCon were assessed by monitoring injection site, body condition and body weight at vaccination, at the booster stage and one year after initial vaccination. At the same times, blood samples were collected to quantify antibodies to the vaccine and to assess pregnancy status. GonaCon did not affect the body weight or body condition of cattle and had no adverse side effects such as injection site reactions, limping or abnormal behaviour. GonaCon did not appear to interrupt ongoing pregnancies but reduced fertility significantly: the proportion of pregnant animals in the GonaCon-treated group decreased from 76% at initial vaccination to 6% one year after vaccination, compared to 67% and 57% respectively in the control group. There was no difference between antibody titres at the booster stage or one year post vaccination, suggesting the booster dose maintained antibody levels. This study confirmed that GonaCon is safe and effective in inducing infertility in feral cattle, with a booster dose critical for maintaining infertility.
GonaCon, a single-shot injectable immunocontraceptive vaccine targeting the gonadotropin-releasing hormone (GnRH), has been tested in key mammal species in the UK and shown to be a safe method to reduce population size in areas of high human wildlife conflict. Badgers exhibit an unusual reproductive physiology in that females may maintain fertilised eggs and dormant blastocysts at any time of year and delay their implantation until the winter. It is thus necessary to evaluate the consequences of delayed implantation and timing of vaccination on the effectiveness of GonaCon for fertility control of female badgers. We found that vaccination in June had an immediate effect on the fertility indicators monitored and inhibited subsequent cub production in the following year, while vaccination in November had no effect. Further results suggest that the optimal vaccination window in badgers could be as narrow as between June and August. The longer-term effectiveness of GonaCon vaccination in female badgers appears to reflect maintenance of anti-GnRH antibody titres at or above a putative threshold titre of 1:128,000, a threshold higher than that reported for other species (1:64,000). While it is possible that using a larger dose (> 1 mL) might lead to longer lasting effects, this study shows that vaccination would need to be repeated at least every 2 years in order to maintain levels of female infertility predicted to have demographic impacts on badger populations. Overall, no negative welfare consequences were observed in vaccinated badgers indicating that GonaCon is a potential tool for the management of conflicts involving badgers.
Increases in human-wildlife conflicts alongside cultural shifts against lethal control methods are driving the need for alternative wildlife management tools such as fertility control. Contraceptive formulations suitable for oral delivery would permit broader remote application in wildlife species. This study evaluated the contraceptive effect and immune response to two novel injectable immunocontraceptive formulations targeting the Gonadotropin Releasing Hormone (GnRH): MAF-IMX294 and MAF-IMX294P conjugates, both identified as having potential as oral contraceptives. The study also explored whether in multiparous species immunocontraceptives may either totally prevent reproduction or also affect litter size. Female rats, chosen as a model species, were given three doses of either MAF-IMX294 or MAF-IMX294P to compare anti-GnRH immune response and reproductive output up to 310 days post-treatment. Both formulations induced anti-GnRH antibody titres in 100% of rats and significantly impaired fertility compared to control animals. Following treatment with MAF-IMX294 and MAF-IMX294P 0 of 9 and 1 of 10 females respectively produced litters following the first mating challenge 45 days post-treatment, compared to 9 of 9 control animals. Across the whole 310 day study period 7 of 9 females from the MAF-IMX294 group and 10 of 10 females in the MAF-IMX294P group became fertile, producing at least one litter throughout six mating challenges. No significant differences were found between the two formulations in antibody titre response or duration of contraceptive effect, with an average time to first pregnancy of 166 days for MAF-IMX294 and 177 days for MAF-IMX294P for all females that became fertile. Following treatment with MAF-IMX294 and MAF-IMX294P the first litter produced post-infertility in treated females was significantly smaller than in control animals. This indicates treatment with immunocontraceptives may induce an overall suppression of fecundity extending past an initial infertility effect. This increases the potential long-term impact of these immunocontraceptives in multiparous species such as commensal rodents.
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