Non-Surgical Approaches

Immunological Approaches

Standard vaccines for dogs and cats (rabies, distemper, leptospirosis, parvovirus, and feline calicivirus, among others) are designed to stimulate the body's immune system to produce antibodies to a particular virus or bacteria. Researchers have explored vaccines to suppress fertility in dogs and cats for several decades, and the basic concept behind an immunological approach to control fertility is similar to efforts to prevent disease: a vaccine stimulates dogs and cats to produce antibodies to key proteins involved in reproduction. When these antibodies are present at certain levels, an animal is infertile. As is the case with most vaccines, however, the effect is not permanent, and "booster" vaccines are necessary for lifetime infertility.

 

To date, researchers have studied two primary targets for immunocontraception. One is gonadotropin releasing hormone (GnRH), sometimes called the “master hormone” because it controls reproductive processes in both males and females and across mammalian species. Without GnRH stimulation, gonadal hormone production is suppressed, and gametes (eggs and sperm) do not mature. By triggering creation of antibodies against GnRH, a vaccine can prevent production of hormones necessary for reproduction—and by extension cause infertility and suppress hormone-driven sexual behaviors. One GnRH vaccine formulation, GonaCon™, has been approved by the Environmental Protection Agency (EPA) for one-year contraception of adult female white-tailed deer, wild horses, and wild burros. Booster vaccines can be given to extend the period of efficacy. GonaCon™ works in males as well, but with less duration. 

A non-cellular membrane, the zona pellucida, surrounds each of a female mammal’s unfertilized eggs. One protein within the zona pellucida is believed to be essential to allowing sperm to attach to the egg. Zona pellucida (ZP) vaccines, limited to female mammals, are designed to stimulate the body to produce antibodies that attach to the sperm receptors of the zona pellucida and block fertilization. A porcine zona pellucida (PZP) vaccine, ZonaStat-H, is EPA-approved for female wild horses and burros. It is important to note that because this approach affects reproduction at the level of the ovaries, it does not suppress estrus or natural sexual behaviors (in contrast to GnRH vaccines).

Returning to our species of interest: dogs and cats. The use of GnRH and PZP vaccines in these species have yielded mixed results. One GonaCon™ formulation has shown promise in male and, especially, female cats; some queens remained infertile for the duration of the 5-year study, and infertility averaged 3.5 years. These results led ACC&D to do a follow-up controlled field study; unfortunately the average duration of effect was too low for us to consider moving the project forward.

In dogs, a GnRH vaccine that produced long-term infertility also caused unacceptable adverse injection site reactions. In female dogs, ZP vaccines, including but not limited to ZonaStat-H, have had inconsistent results on antibody production and have not effectively prevented fertility. They have also not been effective in female cats. In short, efforts to develop immunocontraceptive vaccines that are effective, long-lasting, and safe are ongoing. Michelson Prize research in the field of immunocontraceptives can be found here

GonaCon™ 

GonaCon™ is a GnRH-hemocyanin conjugate immunocontraceptive vaccine developed by the National Wildlife Research Center (NWRC), the research arm of the USDA-APHIS Wildlife Services program. It is designed to prompt an animal to create antibodies against the gonadotropin releasing hormone (GnRH) produced by the body, thus suppressing production of gonadal hormones and maturation of gametes (eggs and sperm).

The vaccine was developed to provide a non-lethal option for controlling wildlife populations. Indeed, it is now approved by the U.S. Environmental Protection Agency (EPA) to contracept adult female white-tailed deer and wild/feral horses and burros for a minimum of one year. Due to the mechanism of action, in addition to preventing reproduction, the vaccine has been found to suppress behaviors driven by sex hormones.

At this point, you might be wondering how a vaccine developed and approved for white-tailed deer, wild horses, and wild burros is relevant to cats and dogs. A reasonable question, indeed! When it comes to the production and effect of GnRH, mammals are quite similar, which means that the vaccine can have the same contraceptive effect on dogs and cats as it does on much larger species. It also has potential for the same contraceptive effect on males as it does on females. 

Various formulations of this immunocontraceptive vaccine have been evaluated in males and females of multiple mammalian species, including cats and dogs. Study findings with one vaccine formulation indicate promise for male and, especially, female cats. Some queens remained infertile for the duration of the five-year study, and the median period of infertility was more than three years. Study results prompted ACC&D to take next steps with this vaccine as a fertility control tool for cats, particularly community and feral populations. Interestingly, cats in a simulated free-roaming cat colony did not respond nearly as well to the vaccine as those in the first study. You can learn more here.

Finding a simultaneously safe and effective formulation for dogs has proven more difficult, unfortunately, as they are one of a small number of species with greater sensitivity to the vaccine adjuvant used to enhance the body’s immune response. The NWRC continues to work to develop a formulation that safely contracepts dogs, recognizing the great potential for contraceptive and rabies vaccines to be given concomitantly to free-roaming dogs and advance humane population and rabies control efforts.