Elsevier

Theriogenology

Volume 76, Issue 8, November 2011, Pages 1517-1525
Theriogenology

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

https://doi.org/10.1016/j.theriogenology.2011.06.022Get rights and content

Abstract

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.

Introduction

Unowned free-roaming (feral) cats number in the millions nationally and exist throughout the world [1]. Their uncontrolled reproduction contributes to cat overpopulation and associated concerns regarding their impact on public health and the environment [2]. In parts of the world where progressive animal control resources are not available, measures such as poisoning and shooting are still used to control cats [3]. Surgical sterilization followed by return to the colony is an increasingly popular method of controlling feral cat populations, but is expensive, labor-intensive, highly technical, and limited in scale [4], [5].

Nonsurgical fertility control that could be administered to feral cats in the field would be a powerful tool for cat population control. Control of free-roaming species is often aimed at the level of the population, rather than at specific individual animals. Treatment must be efficacious in a high proportion of the population, but it is not essential that every treated animal be rendered infertile. Feral cats are wary of humans, and once trapped and released, are unlikely to return for repeated trapping episodes. A practical fertility control technique for feral cats would induce permanent or multi-year duration of action following a single treatment in the majority of animals treated.

Vaccines aimed at reproductive targets are one approach to nonlethal control of overabundant free-roaming species. Overcoming tolerance to self antigens and induction of durable immunity without the use of repeated booster vaccines are substantial challenges for the development of immunocontraceptive vaccines. A commonly used contraceptive antigen in wildlife is the zona pellucida. In previous studies, we demonstrated that vaccinating against the zona pellucida was ineffective in preventing pregnancy in cats [6], [7]. Subsequently, we showed in a short-term study that a single dose of GnRH vaccine in a mycobacterial and oil emulsion (GonaCon™) effectively blocked testosterone production and spermatogenesis for at least 6 mo in a majority of vaccinated adult male cats [8]. This was apparently the first report to suggest that fertility control may be achievable in cats following a single vaccination against a reproductive self antigen.

We hypothesized that long-term fertility control in cats can be induced by immunological blockade of GnRH activity. The purpose of this study was to test the efficacy and duration of activity of single-dose GnRH immunocontraception on the fertility of adult female cats.

Section snippets

Cats

Twenty-four 8- to 14-mo-old specific-pathogen-free female domestic shorthair cats were acquired from a commercial vendor (Liberty Research, Waverly, NY, USA). Cats were group-housed in one large enriched room with raised resting benches, maintained at ambient temperatures between 21 and 23 °C, and exposed to controlled lighting (explained later). Food and water were available ad libitum. The experimental design was approved by the University of Florida Institutional Animal Care and Use

Reactions to treatment

Body temperature in all of the cats remained normal after treatment, and there was no inflammation or tenderness at the injection sites. One vaccinated cat died suddenly 45 d after treatment; necropsy revealed no gross or histological abnormalities to explain the death. This cat was replaced with a 2 y old cat of proven fertility from the colony and vaccinated with the GnRH vaccine according to the standard protocol.

Twenty-four months after immunization, it was discovered that one of the cats

Discussion

The vaccine used in this study induced fertility control in 100% of cats following a single injection, but duration of contraception varied from 5 mo to > 5 y. Infertility was maintained for 3 y in approximately half of the cats and for more than 5 y in a quarter of the cats. Response to vaccination was accompanied by a cessation in estrous cyclicity and with weight gain, similar to cats undergoing surgical sterilization via ovariectomy.

This is apparently the first study to demonstrate

Acknowledgments

Supported by a grant from the Morris Animal Foundation.

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