Naz Rajesh K
Reproductive Immunology and Molecular Biology Laboratories, Department of Obstetrics and Gynecology, West Virginia University, School of Medicine, Morgantown, WV 26506-9186, USA.
Am J Reprod Immunol. 2009 Jan;61(1):11-8. doi: 10.1111/j.1600-0897.2008.00663.x.
This is a review of anti-sperm contraceptive vaccines (CV), and synthesis of human scFv antibodies that can be used as immunocontraceptives.
Various methods of proteomics and genomics, peptide synthesis, phage display technology, and antibody engineering were used to obtain multi-epitope vaccines and human scFv antibodies from immunoinfertile and vasectomized men. The present review primarily focuses on the effect of multi-epitope vaccines and Izumo on fertility, and synthesis and characterization of sperm specific human scFv antibodies.
The immunization with Izumo peptides causes a contraceptive effect in female mice. The efficacy is enhanced by combination vaccination, including peptides based on other sperm antigens. Using phage display technology, we were able to synthesize at least four novel scFv antibodies with unique complementarity determining regions (CDRs) that reacted with specific fertility-related sperm antigens. These antibodies inhibited human sperm function in vitro, and their immunocontraceptive effect in vivo by these antibodies is currently being investigated.
The multi-epitope vaccines may provide an efficacious and viable approach to contraception. The human scFv antibodies, if they block fertility in vivo, may provide unique and novel immunocontraceptives, the first of its kind for human use. The multi-epitope CV and preformed engineered antibodies of defined specificity may obliterate the concern related to inter-individual variability of the immune response.
本文综述了抗精子避孕疫苗(CV)以及可作为免疫避孕药使用的人源单链抗体片段(scFv)的合成。
运用蛋白质组学和基因组学、肽合成、噬菌体展示技术及抗体工程等多种方法,从免疫性不育和接受输精管切除术的男性中获取多表位疫苗和人源scFv抗体。本综述主要聚焦于多表位疫苗和 Izumo 对生育能力的影响,以及精子特异性人源scFv抗体的合成与表征。
用 Izumo 肽免疫可使雌性小鼠产生避孕效果。联合接种包括基于其他精子抗原的肽可增强疗效。利用噬菌体展示技术,我们能够合成至少四种具有独特互补决定区(CDR)的新型scFv抗体,它们能与特定的生育相关精子抗原发生反应。这些抗体在体外抑制了人类精子功能,目前正在研究它们在体内的免疫避孕效果。
多表位疫苗可能为避孕提供一种有效且可行的方法。人源scFv抗体若能在体内阻断生育能力,可能会提供独特新颖的免疫避孕药,这是首例供人类使用的此类药物。多表位CV和具有明确特异性的预制工程抗体可能消除与免疫反应个体间变异性相关的担忧。