THE AMERICAN MUSTANG


formulation to meet the needs of large scale reduc- tion of free-ranging horse populations. Although all three formulations are pZP-based, two formula- tions, a liquid pZP emulsionh and pZP-22 (a pelleted form of pZP) use pZP harvested from pig ovaries similarly whereas a third pZP-based vaccinei,ispro- duced slightly different. Additionally, pZP incorpo- rated in liposomesi incorporates a diffusion-release mechanism (lipid bilayer liposomes). PZP-22 uses liquid pZPh as a primary inoculation and pellets containing pZP incorporated in d-lactide-glycolide copolymers as a controlled, time-release mechanism and QA-21 as the adjuvant for long-acting, booster effects when administered as a paired injection. Liq- uid pZPh is not formulated with controlled release mechanisms and must be administered on a yearly basis to maintain long-term contraceptive effect. The differences in methods of production of pZP from pig ovaries as well as the formulations for long-term effects may be related to the differences in results obtained when used as contraception agents. In particular, the differences between long-term and adverse effects are evident when pZP incorpo- rated in liposomesi is administered in comparison with liquid pZP and pZP-22. In general, the major differences are related to effects on follicular devel- opment, uterine pathology, and reversibility post- inoculation. Reductions in the number and sizes of follicular development and persistent uterine edema have been reported after the administration of alternate formulations of pZP incorporated in liposomesi.29,36 In addition, evidence of reversibility of the contraceptive effect after the administration of pZP incorporated in liposomesi have not been consistently observed or reported. Although oocyte evaluation was not performed, the use of liquid pZPh also reported a decline in ovarian estrogen produc- tion and ovulation rates in treated mares after 3 to 7 years of consecutive yearly injections of the agent. The rate of decline for ovulations reached 10% af- ter seven consecutive years of treatment. In this study, the absence of ovulation was determined by an assay for nonspecific progesterone metabolite iPdG assay from fecal samples.37 No effects on cy- clicity in the mare have been reported as yet after the use of pZP-22. However, further investigations are required to evaluate its effect on cyclicity in the mare post-injection. It is speculated that disrup- tion of cyclicity of mares post pZP treatment may be 1) due to the presence of other ovarian proteins present in the inoculate, in view of the manner in which pZP is currently being processed and used and 2) additional mechanisms of infertility induced by pZP other than blocking of attachment of the zona pellucida by steric hindrance. Injection site abscesses have also been reported following the use of liquid pZPh and pZP-22.38 In this study, significantly large numbers of abscesses, nodules, and transient swellings were found in mares when pZP was remotely delivered with a rifle. Hand injection of the agent, in contrast, produced


minimal numbers of presumptively granulomatous nodules at the injection site. The contraceptive effectiveness of pZP-based vac-


cines vary considerably throughout the literature and may lead to much confusion among the reading audience. In general, however, pZP-based vaccines are considered to be 85% to 100% effective for the first year. With long-acting, single injection formu- lations, the effectiveness begins to decrease after the second and third years at a range of 83% to 85% and 68% to 85%, respectively.29,39 Unfortunately, recent unpublished data using pZP (pZP-22 and pZP incor- porated in liposomesi) designed for long-acting con- traceptive effects as well as a GnRH vaccineb, have provided evidence of suboptimal and inconsistent results compared with those previously reported (Kane A, personal communication). Variations in results using similar or modified formulations of pZP-based agents may be attributable to a host of factors, such as delivery method (hand injection, jab-stick injection, remote delivery), alteration of formulations for long-term effects, adjuvant modifi- cations, methods for monitoring, personnel admin- istering of the vaccine, health and nutritional status of the mares, accurate identity of the vaccinated mares, and other uncontrollable factors in free-rang- ing horse management that may influence or limit the outcome of obtaining optimal and consistent results. Many studies have emerged and have been re-


ported in the literature on the successful use of liquid pZP,h as a fertility control agent. However, a major disadvantage of this pZP formulation is that it requires repeated injections on a yearly basis to maintain contraceptive effect in the mare. From a free-ranging, feral horse management perspective, the necessity to inoculate any mare on a yearly basis to achieve effective contraception on a long-term basis would likely be considered impractical. Liq- uid pZPh and pZP-22 have demonstrated safety for use in mares with no apparent short term, adverse effects with the exception of limited nodule forma- tion at the injection site post-treatment.38,39 Use of liquid pZPh after several consecutive years has also been reported to reduce ovarian estrogen production and ovulation in treated mares as mentioned pre- viously. Despite these disadvantages, liquid pZPh and pZP-22 is safe for use in pregnant mares,40 evidence for reversibility after inoculation has been reported,41 pZP in inoculated animals will not pass along the food chain,42 and there are no detrimental behavior changes in inoculated mares.43,44 Addition- ally, it has been shown that mares inoculated with liquid pZPh on a yearly basis improve the overall body condition and longevity of the mares.45 Concerns that pZP inoculated mares may cause


an extension of the breeding season have been raised. The treated mares’ failure to conceive but continue to cycle normally, thereby causing exces- sive out-of-season activity of stallions and the pro- duction of out-of-season foals past the normal


AAEP PROCEEDINGS  Vol. 60  2014 429


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