The research had focused on the use of two approved microbial vaccine strains originally developed to help prevent Salmonella and rabies infections in animals. Researchers at CMMID engineered into these vaccine strains a gene encoding a protein encoding either the swine or rabbit zona pellucida (ZP) surrounding the vertebrate eggs. When used as an oral vaccine, both the Salmonella and rabies vaccine were shown to trigger the production of antibodies against the proteins encoded by genes engineered into the vaccines. These strains were fed to female cats to assess if they were capable of inducing antibodies that prevented or reduced conception.

Vaccine Trials: Over several years in separate studies of female cats fed orally either of the engineered strains (Salmonella or vaccinia expressing swine ZP), it was concluded that neither vaccine induced sufficient immune responses that caused contraception. This was in spite of showing that there were specific antibodies produced that recognized the ZP antigen or the microbe expressing the ZP, i.e. antibodies against Salmonella or vaccinia. Even though the dosing was performed under highly controlled laboratory conditions, individual cats responded very differently ranging from little to moderate responses. This means that the routine use of Salmonella/ZP or vaccinia/ZP in the field to treat feral cats is more problematic as one has no way of controlling the dose they receive. Moreover, in the case of vaccinia, a single exposure to the virus induces a long- lived immunity that prevents them being boosted with a second dose. We have stopped developing Salmonella and vaccinia as a delivery platform for a contraceptive antigen in feral cats.

Current Directions: We have finished producing a recombinant contraceptive antigen consisting of GnRH fused to a very strong adjuvant to that it can be produced in the laboratory and is 10 fold less expensive that a commercially synthesized version. It is being tested in purpose bred mice for use as an injectable. We are also moving the gene encoding this contraceptive antigen into USDA approved vaccine strain of feline herpes virus (FHV) vaccine strain. A GnRH subunit vaccine (administered as an injectable) has been shown at the veterinary colleges at Auburn University and the University of Florida to induce infertility in cats. The published use of FHV as a delivery system for vaccination has been successful for other antigens. We face the same hurdles with any FHV expressing GnRH as we did with the vaccinia virus or Salmonella expressing ZP. Is the immune response elicited by an oral route sufficient to block conception and can the vaccine be made specific for felines? According to the literature, the herpes viruses are extremely host adapted such that in principle FHV will only infect cats. We are in the process of testing whether indeed the FHV host range is restricted to cats.

Meetings: We held our second International Symposium on Nonsurgical Methods for Pet Population Control on June 24-27, 2004, in Breckenridge, CO (see ACCD web site (http://www.acc-d.org/) for symposium proceedings). Over 125 attendees convened, representing scientists, foundations, pharmaceutical companies, and animal welfare organizations and advocates, traveling from 12 countries and 24 U.S. states. The agenda ranged from the science to the practical aspects of bringing solutions to market. Our 3rd International Symposium is being planned for November 2006 - see the ACCD web site for details.

Funding/Personnel: Funds have been received from several foundations that have allowed us to hire research personnel; in addition, some of these funds are being used to hire veterinary students interested in helping develop and test the vaccines. A graduate student is pursuing a M.Sc. research program to assess the utility of FHV to delivery contraceptive antigens to cats.

Donations: Individuals or organizations interested in donating money to support this research at Virginia Tech should contact: Dr. Frank Pearsall, Director of Development, Virginia- Maryland Regional College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, 24061 (540-231-4259; pearsall@vt.edu). For any further information on the vaccine, contact S.M. Boyle (540-231-4641; smboyle@vt.edu)

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Stephen M. Boyle
Professor of Microbiology
Center for Molecular Medicine and Infectious Diseases
Virginia-Maryland Regional College of Veterinary Medicine
Virginia Tech
Blacksburg, Virginia 24061-0342