Reproductive Immunology and Molecular Biology Laboratories, Department of Obstetrics and Gynecology, The West Virginia University, School of Medicine, Morgantown, WV 26506-9186, USA.
J Reprod Immunol. 2009 Dec;83(1-2):145-50. doi: 10.1016/j.jri.2009.06.260. Epub 2009 Oct 23.
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.
避孕疫苗针对精子是一个令人兴奋的提议。这篇综述集中讨论了抗精子避孕疫苗和基因工程人抗体，这些抗体可作为免疫避孕药使用。为了从免疫不育和输精管结扎的男性中获得多表位避孕疫苗和人单链可变片段（scFv）抗体，已经使用了各种疫苗学和抗体工程方法。由各种精子抗原、肽表位或 DNA 组成的避孕疫苗在小鼠模型中显示出不同程度的可逆避孕效果，并且其功效随着多表位组合疫苗的使用而增强。未能实现完全的生育阻断可能是由于宿主免疫反应的可变性。利用噬菌体展示技术，我们的实验室已经在体外合成了至少四种具有独特互补决定区（CDRs）的新型 scFv 抗体，这些抗体与来自免疫不育和输精管结扎的男性的 cDNA 中特定的与生育相关的精子抗原反应。这些抗体在体外抑制人精子功能，正在研究其体内免疫避孕效果。如果这些人 scFv 抗体在体内阻断生育能力，它们可能提供独特而新颖的免疫避孕药，这是人类首次使用。多表位避孕疫苗和预先确定特异性的工程化抗体可能消除与免疫反应个体间变异性相关的担忧。
