Institute of Immunology, PLA Department of Obstetrics and Gynecology, Southwest Hospital, Third Military Medical University, 30 Gaotanyan Street, Shapingba District, Chongqing 400038, People's Republic of China.
Reproduction. 2011 Nov;142(5):659-66. doi: 10.1530/REP-11-0161. Epub 2011 Sep 9.
SPINLW1 (previously known as eppin (epididymal protease inhibitor)) is a target under intense scrutiny in the study of male contraceptive vaccines. B-cell-dominant epitopes are now recognized as key parts of the induction of humoral immune responses against target antigens. The generation of robust humoral responses in vivo has become a crucial problem in the development of modern vaccines. In this study, we developed a completely novel B-cell-dominant-epitope-based mimovirus vaccine, which is a kind of virus-size particulate antigen delivery system. The mimovirus successfully self-assembled from a cationic peptide containing a cell-penetrating peptide of TAT49-57 and a plasmid DNA encoding both three SPINLW1 (103-115) copies and adjuvant C3d3. The male mice were immunized with the epitope-based mimovirus vaccine, which resulted in a gradual elevation of specific serum IgG antibody levels. These reached a peak at week 4. Mating for the fertility assay showed that the mimovirus vaccine had accomplished a moderate fertility inhibition effect and investigation into the mechanism of action showed that it did so by interfering with the reproductive function of the sperm but that it did not damage the structures of the testes or cause serum testosterone to decline. Our results suggest an ideal protocol for suppressing fertility in mice by an engineered mimovirus vaccine.
SPINLW1（以前称为 eppin（附睾蛋白酶抑制剂））是男性避孕药研究中备受关注的靶点。B 细胞优势表位现在被认为是诱导针对靶抗原的体液免疫反应的关键部分。在体内产生强大的体液免疫反应已成为现代疫苗发展的关键问题。在这项研究中，我们开发了一种完全新型的基于 B 细胞优势表位的拟病毒疫苗，它是一种病毒大小的颗粒抗原传递系统。拟病毒成功地自组装自一种阳离子肽，该肽含有 TAT49-57 的穿透肽和编码三个 SPINLW1（103-115）拷贝和佐剂 C3d3 的质粒 DNA。雄性小鼠用基于表位的拟病毒疫苗进行免疫，导致特异性血清 IgG 抗体水平逐渐升高。这些在第 4 周达到峰值。用于生育能力测定的交配表明，拟病毒疫苗已经实现了中等的生育抑制效果，并且作用机制的研究表明，它通过干扰精子的生殖功能来实现，但不会损害睾丸结构或导致血清睾酮下降。我们的结果表明，通过工程拟病毒疫苗抑制小鼠生育能力的理想方案。
