EQUINE EQUINE 39 Blackwell Publishing Asia Suppression of behavioural and physiological oestrus in the mare by vaccination against GnRH M ELHAY, a A NEWBOLD, a A BRITTON, a P TURLEY, b K DOWSETT, c and J WALKER a Objective To examine the immunogenicity of an equine immunocontraceptive vaccine and its efficacy in controlling hormone-related behaviour. Design A total of 24 mares at two sites in Australia were vac- cinated with an immunocontraceptive vaccine comprising gonadotrophin releasing hormone (GnRH) conjugated to a carrier protein in immunostimulating complex as an adjuvant. Twelve animals at each site received a placebo of adjuvant alone and served as controls for seasonal oestrus, hormonal and behaviour patterns. Animals were observed for injection site reactions, ovarian and follicular activity, and serum levels of antibody, 17β-oestradiol and progesterone in the weeks fol- lowing vaccination. Mares were also examined for oestrous behaviour by teasing with a stallion. Results All mares responded to vaccination. Two weeks following the second vaccination there was a peak in antibody response to GnRH that declined gradually over the following weeks. Commensurate with the elevated anti-GnRH antibody there was a marked effect on ovarian activity with a reduction in 17β-oestradiol and progesterone levels in the 24 vaccinated mares. There was also a reduction of oestrus-related behaviour as determined by a teaser stallion. This effect lasted a minimum of 3 months and correlated with the initial level of antibody response. Conclusion Following a conventional two-dose immunisa- tion regime this commercially available equine immunocontra- ceptive vaccine was effective at inhibiting oestrous behaviour for at least 3 months. This vaccine has a high level of safety since there were no significant local reactions nor were there any adverse systemic responses to vaccination. Key words: vaccination, gonadotrophin releasing hormone, mares, equine reproduction Aust Vet J 2007;85:39–45 doi: 10.1111/j.1751-0813.2006.00092.x EIA Enzyme immunoassay FSH Follicle stimulating hormone GnRH Gonadotrophin releasing hormone LH Luteinising hormone TU Titre unit(s) T he onset of oestrus in mares and fillies is often associated with behavioural changes such as leaning, urinating, aggressiveness and responsiveness to nearby stallions that can cause considerable concern to the animal’s owner, trainer or handlers. Gonadotrophin releasing hormone (GnRH) has a central role in the control of fertility and sexual behaviour in mammals and thus oestrous behaviour in mares. GnRH exerts this effect indirectly by controlling the release of follicle stimulating hormone (FSH) and luteinizing hormone (LH) from the anterior pituitary. Disruption of the effects of GnRH by manipulation of GnRH receptor signals either by agonists or antagonists, has raised concerns about their expense and/or longevity of effect. 1 Neutralisation of GnRH by specific antibody elicited by vaccination represents an alternative approach and should lead to a dramatic reduction in levels of FSH and LH and subsequent effects on gonadal function. Previously, studies with experimental formulations have demon- strated that vaccination against GnRH can have significant effects on reproductive function of colts and stallions 1–6 and prevention of the development of oestrus in the mare. 1,7–11 These studies demonstrated the feasibility of immuno-contraception in male and female horses, confirming significant physical and endocrine effects. The immunocontraceptive effects of these vaccines were often observed only following repeated, prolonged immunisation regimes that were often associated with unaccept- able site reactions. There is a need, therefore, for an immunocon- traceptive vaccine that would be effective and have an acceptable safety profile for general use in horses. The feasibility of developing GnRH vaccines for use in domestic species has now been established in the swine 12 where such a vaccine is used to control boar taint in uncastrated male pigs. This vaccine has the additional benefit that it increases production gains and improves carcass characteristics, primarily through its action in suppressing sexual behaviour including fighting. A natural exten- sion of this observation in pigs would be to apply this technology to other species where control of sexual behaviour is desired. Materials and methods Animals Mares aged between 3 and 12 years were obtained at sales in South Eastern Queensland or leased from a horse buyer in Victoria (24 mares per site). The reproductive status of each mare was assessed by rectal examination and ultrasonography, before mares were admitted into the trial, to ensure they were cycling. For teasing, a miniature stallion (Queensland) or a Shetland pony stallion (Victoria) was used. Experimental location and timing Two trials were run in the late spring to early summer in two locations. Study 1 was conducted at Woodhill, Queensland (latitude 27°53′S) starting on 5 October 1999. Study 2 at a Veterinary Medicines Research and Development, Pfizer Animal Health, Parkville VIC 3052, Martin.Elhay@pfizer.com b Woodhill Veterinary Surgery, Woodhill QLD 4285 c Southerden Avenue Consulting, Grange QLD 4051 © 2007 Pfizer Australia Australian Veterinary Journal Volume 85, Nos 1 & 2, January, February 2007 Journal compilation © 2007 Australian Veterinary Association