Infertility in female rabbits (Oryctolagus cuniculus) alloimmunized with the rabbit zona pellucida protein ZPB either as a purified recombinant protein or expressed by recombinant myxoma virus

Development of immunocontraceptives for wild rabbit populations requires se lection of both effective antigens and effective delivery systems. Recombin ant rabbit zona pellucida glycoprotein B (ZPB) produced in eukaryotic cells in vitro was an effective antigen and induced sustained infertility in 70% of female rabbits. This required two boosts and serum antibody titers of 1 2 800 or greater. Antibody titers in females were low after the initial imm unization, as might be expected with a self-antigen; however, male rabbits had a strong antibody response, indicating that the protein was immunologic ally foreign. To develop a delivery system, ZPB was delivered by infection with a recombinant myxoma virus. In contrast to the results with ZPB protei n, infection of rabbits induced a similar serum antibody response to ZPB in both sexes. This indicated that presentation of ZPB in the context of a vi rus infection was able to overcome tolerance in females. However, the antib ody titers were lower than 12 800, and only 25% of female rabbits were infe rtile. This antibody response was boosted by injections of recombinant ZPB protein, after which 80% of female rabbits were infertile. Infertility was associated with antibody binding to zonae and varying degrees of ovarian pa thology characterized by follicular degeneration and substantial depletion of primordial follicles. Oocyte and follicular degeneration appeared to be the principal mechanism of infertility and may be primarily induced by anti bodies to ZPB.