Development of genetically engineered human sperm immunocontraceptives.

摘要

Contraceptive vaccines targeting sperm are an exciting proposition. This review is focused on anti-sperm contraceptive vaccines and genetically engineered human antibodies that can be used as immunocontraceptives. Various methods of vaccinology and antibody engineering have been used to obtain multi-epitope contraceptive vaccines and human single chain variable fragment (scFv) antibodies from immunoinfertile and vasectomized men. Contraceptive vaccines comprised of various sperm antigens, peptide epitopes or DNA have shown various degrees of reversible contraceptive effect in the mouse model and their efficacy is enhanced with the multi-epitope combination vaccine. Failure to achieve a complete fertility block is probably due to variability in the host immune response. Using phage display technology, our laboratory has synthesized in vitro at least four novel scFv antibodies with unique complementarity determining regions (CDRs) that react with specific fertility-related sperm antigens employing cDNA from immunoinfertile and vasectomized men. These antibodies inhibit human sperm function in vitro, and their immunocontraceptive effect in vivo is being investigated. If these human scFv antibodies block fertility in vivo they may provide unique and novel immunocontraceptives, a first-in-kind for human use. The multi-epitope contraceptive vaccines and preformed engineered antibodies of defined specificity may eliminate concern related to inter-individual variability of the immune response.