Domestic Cat Contraception Using a Single-Dose, Micro-Encapsulated LHRH Vaccine.

In the U.S., 30 to 100 million cats are estimated to survive in a feral environment, representing a major health, environmental and welfare issue. A single-dose contraceptive vaccine has several potential applications in felids, most notably for control of feral cat populations. In this study, we evaluated the safety and effectiveness of a single-dose luteinizing hormone-releasing hormone (LHRH) vaccine for contraception in cats. The vaccine was comprised of a recombinant ovalbumin-LHRH (ova-LHRH) fusion protein as the antigen mixed with adjuvant containing cytosine guanine oligodeoxynucleotide (CpG ODN). The single-dose vaccine contained both non-encapsulated and encapsulated forms of ova-LHRH; the latter presented the antigen in agarose microbeads for slow release. Fifteen young adult, intact female cats were randomly assigned to one of the following treatment groups (n=5 cats/group): 1) two injections of non-encapsulated ova-LHRH (350 μg each), 8 weeks apart (positive control); 2) one injection of a mixture of encapsulated (440 μg) and non-encapsulated (350 μg) ova-LHRH; and 3) one injection of saline (negative control). Injection sites were monitored for inflammatory responses. Blood samples were collected bi-weekly for one year, and LHRH antibody production assessed using a validated radioimmunoassay. Progestin metabolite profiles were monitored via a validated enzyme immunoassay in fecal samples collected every 2 to 3 days for one year. Fertility was assessed by housing a proven breeder male with females for four months beginning six months after initial injection. In the saline group, percent binding of 125I-LHRH in serum was zero throughout the study. At the end of the study (weeks 38-44 post-injection), antibody binding activity was higher (P < 0.05) in the two-dose group (63.4% ± 9.8; mean ± SEM) compared to the single-dose group (27.0% ± 7.9). Prior to immunization, all 15 females exhibited estrual behavior indicative of ovarian cyclicity, and most females (13/15) appeared to be spontaneous ovulators based on elevated fecal progestin levels lasting 5 weeks or longer. In the saline group, all five females continued to ovulate spontaneously throughout the study until pregnancy. In the single-dose group, four of five females were no longer ovulating by the beginning of the fertility trial; however, one of these four resumed ovulatory activity towards the end of the trial and became pregnant. The remaining female in this group ovulated regularly until pregnancy. In the two-dose group, three of five cats were spontaneous ovulators initially; all three ceased ovulating by the time of the fertility trial. One of these cats showed elevated progestin levels towards the end of this time period, but did not become pregnant. All females (5/5) in the saline group became pregnant (kittens/litter, 3.6; litter size, 1-5). No pregnancy occurred in the two-dose group. In the single-dose group, two of five females became pregnant (litter size, 3-4). Subcutaneous granulomas were observed at the injection sites in all immunized females, with the most severe granulomas occurring in the two-dose group including two with ulceration. Granulomas reduced in size spontaneously but were still palpable one year after injection. In conclusion, the single-dose LHRH vaccine provided some fertility control but adjustment of dose and/or delivery system may be needed for more consistent, long-lasting contraception. (Morris Animal Foundation grant # D08FE-029). (platform)