Immunologic behavior of human cysteine-rich secretory protein 1 (hCRISP1) in primates: prospects for immunocontraception

Objective: To evaluate the immunologic behavior of human cysteine-rich secretory protein 1 (hCRISP1), a human sperm epididymal protein involved in fertilization, to establish its immunocontraceptive potential. Design: In vivo study in a nonhuman primate model. Setting: Animal care facility of an academic research center. Animal(s): Adult (6- to 15-year-old) male and female cynomolgus macaques (Macaca fascicularis) distributed into three groups. Intervention(s): Animals received four injections (intramuscularly) of recombinant hCRISP1, recombinant monkey CRISP1 (mkCRISP1), or maltose-binding protein (MBP). Blood and semen samples were obtained before and after immunization. Main Outcome Measure(s): Anti-hCRISP1 and anti-mkCRISP1 levels in sera and seminal plasma were evaluated by enzyme-linked immunosorbent assay (ELISA). The specificity of the immune response was evaluated by Western blot and binding of the antibodies to sperm by immunofluorescence. Result(s): Both hCRISP1 and mkCRISP1 raised an immune response that increased as a function of time and specifically recognized mkCRISP1 in sperm extracts. Sperm number, motility, and morphology were not affected by immunization. The presence of both specific antibodies in seminal plasma and a fluorescent labeling in sperm exposed only to second antibody indicated the ability of the anti-hCRISP1 antibodies both to enter into the male reproductive tract and to bind to the cells in vivo. Conclusion(s): These results support the potential involvement of anti-hCRISP1 antibodies in human immunoinfertility and hCRISP1 as a likely candidate for immunocontraception.