Induction of specific immune response and suppression of fertility by B-cell-epitope-based mimovirus vaccine.
Induction of specific immune response and suppression of fertility by B-cell-epitope-based mimovirus vaccine.
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DOI：
10.1530/rep-11-0161
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发表时间：
2011-11
期刊：
影响因子：
3.8
通讯作者：
Zi-gang Shen;Weifeng He;Ji Zhang;Hai-yang He;Xia Yang;Zhengtao Chen;Ping Yang;Jian Li;Z. Liang;Yuzhang Wu;Jin-tao Li
中科院分区：
文献类型：
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作者：
Zi-gang Shen;Weifeng He;Ji Zhang;Hai-yang He;Xia Yang;Zhengtao Chen;Ping Yang;Jian Li;Z. Liang;Yuzhang Wu;Jin-tao Li
SPINLW 1（以前称为eppin（附睾蛋白酶抑制剂））是男性避孕疫苗研究中受到严格审查的目标。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应答的关键部分。体内产生强有力的体液反应已成为现代疫苗开发中的一个关键问题。在本研究中，我们开发了一种全新的基于B细胞优势表位的模拟病毒疫苗，这是一种病毒大小的颗粒抗原递送系统。模拟病毒成功地自组装的阳离子肽含有TAT 49 -57的细胞穿透肽和质粒DNA编码的三个SPINLW 1（103-115）拷贝和佐剂C3 d3。用基于表位的模拟病毒疫苗免疫雄性小鼠，这导致特异性血清IgG抗体水平逐渐升高。这些在第4周达到高峰。生育力试验的交配表明，模拟病毒疫苗具有中度生育力抑制作用，对作用机制的研究表明，其通过干扰精子的生殖功能而实现，但不会损害睾丸结构或导致血清睾酮下降。我们的研究结果表明，一个理想的协议，抑制小鼠生育的工程模拟病毒疫苗。
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.