IMMUNIZATION OF MONKEYS WITH RECOMBINANT COMPLEMENTARY DEOXYRIBONUCLEIC-ACID EXPRESSED ZONA-PELLUCIDA PROTEINS

Objective: To evaluate the effects of immunization with zona pellucida (ZP) proteins produced by recombinant complementary DNA (cDNA) technology for the elicitation and antibodies that inhibit sperm binding without altering ovarian function in the nonhuman primate. Design: Controlled nonhuman primate study. Setting: Controlled environment with individual housing of monkeys in facility approved by National Institutes of Health (NIH) guidelines. Participants: Monkeys housed and treated according to NIH regulations. Interventions: Monkeys immunized and boosted at regular intervals with ZP proteins produced using recombinant cDNA techniques. Main Outcome Measure: Urinary estrogen, P, serum antibody levels, sperm-ZP binding, and ovarian morphology. Results: Monkeys immunized with a recombinant rabbit 75-kd ZP protein expressed from a partial cDNA in the pEX bacteria expression system produce antibodies that interfere with ovarian follicular development and ovarian cyclicity. On the contrary, monkeys immunized with a recombinant rabbit 55-kd ZP protein develop antibodies that inhibit homologous sperm binding but do not affect ovarian follicular development or subsequent ovarian hormonal cyclicity. Conclusion: Monkey antibodies to the rabbit 75-kd ZP recombinant protein can be generated that inhibit ovarian cyclicity as desired for animal sterilization vaccines. Antibodies to the 55-kd ZP recombinant protein inhibit homologous monkey sperm binding to the ZP without altering ovarian endocrine function or morphology as is desired for human immunocontraception.