Construction and evaluation of replication-defective recombinant optimized triosephosphate isomerase adenoviral vaccination in Schistosoma japonicum challenged mice
Construction and evaluation of replication-defective recombinant optimized triosephosphate isomerase adenoviral vaccination in Schistosoma japonicum challenged mice
复制标题
日本血吸虫攻击小鼠复制缺陷型重组优化磷酸丙糖异构酶腺病毒疫苗接种的构建和评估
DOI：
10.1016/j.vaccine.2013.12.059
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发表时间：
2014-02-07
期刊：
影响因子：
5.5
通讯作者：
Su, Chuan
中科院分区：
文献类型：
--
作者：
Dai, Yang;Wang, Xiaoting;Su, Chuan
血吸虫病是一种地方性人畜共患寄生虫病，在中国仍然是一个公共卫生问题。因此，迫切需要研制阻断日本血吸虫传播的兽用疫苗。复制缺陷型腺病毒载体是一种高效的疫苗递送系统，已得到广泛应用。它的使用与高水平的基因插入和表达有关。它易于建造和准备，并且安全。目前尚不清楚这种递送系统是否能提高单克隆抗体疫苗接种的保护作用。磷酸丙糖异构酶。日本血吸虫（SjTPI）是一种很有前途的疫苗候选者。到目前为止，它只在动物模型中诱导了部分保护作用，需要进一步加强才能有效。我们构建了一个复制缺陷型腺病毒载体为基础的疫苗与优化的SjTPI（rAdV-SjTPI.opt）。评价了小鼠的特异性免疫应答和保护效率。结果表明，肌肉注射rAdV-SjTPI.opt可诱导Th 1型免疫应答，而皮下注射rAdV-SjTPI.opt可诱导Th 2型免疫应答。口服rAdV-SjTPI.opt诱导低水平的免疫应答，没有显著的保护作用。肌肉注射rAdV-SjTPI.opt在小鼠中提供了一致且可重复的较高保护作用（超过50%）。这些发现可能是由于相关的较高水平的特异性Th 1，抗体应答和部分较低水平的IL-17 A。该报告为在大型动物中开发阻断传播的兽用疫苗提供了基础。(C)2013爱思唯尔有限公司保留所有权利。
Schistosomiasis is an endemic, zoonotic parasitic disease that remains a public health concern in China. Development of transmission blocking veterinary vaccines against Schistosoma japonicum infection is urgently needed. Replication-defective adenoviral vector is an efficient vaccine delivery system that has been widely used. Its use is associated with high levels of gene insertion and expression. It is easy to construct and prepare, and is safe. It is not known whether this delivery system can improve the protective effect of schistosome vaccination. Triosephosphate isomerase from S. japonicum (SjTPI) is a promising vaccine candidate. Thus far it has induced only partial protection in animal models and needs to be further enhanced to be effective. We constructed a replication-defective adenoviral vector-based vaccine with optimized SjTPI (rAdV-SjTPI.opt). The specific immune responses and protective efficiency in mice were evaluated. Results showed that intramuscular rAdV-SjTPI.opt induced Th1 biased immune responses in the host, while subcutaneous rAdV-SjTPI.opt induced Th2 predominant immune responses. Oral rAdV-SjTPI.opt induced low levels of immune responses and no significant protection. Intramuscular rAdV-SjTPI.opt provided a consistent and repeatable higher protective effect in mice (more than 50%). These findings may be due to the associated higher levels of specific Th1, antibody responses and partially lower level of IL-17A. This report provides a foundation for developing transmission-blocking veterinary vaccines in larger animals. (C) 2013 Elsevier Ltd. All rights reserved.