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用表达呼吸道合胞病毒融合糖蛋白的复制缺陷型腺病毒载体进行鼻内免疫可在BALB/c小鼠中引发保护性免疫。

Intranasal immunization with a replication-deficient adenoviral vector expressing the fusion glycoprotein of respiratory syncytial virus elicits protective immunity in BALB/c mice.

作者信息

Fu Yuanhui, He Jinsheng, Zheng Xianxian, Wu Qiang, Zhang Mei, Wang Xiaobo, Wang Yan, Xie Can, Tang Qian, Wei Wei, Wang Min, Song Jingdong, Qu Jianguo, Zhang Ying, Wang Xin, Hong Tao

机构信息

Institute of Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.

出版信息

Biochem Biophys Res Commun. 2009 Apr 17;381(4):528-32. doi: 10.1016/j.bbrc.2009.02.075. Epub 2009 Feb 20.

DOI:10.1016/j.bbrc.2009.02.075
PMID:19233131
Abstract

Human respiratory syncytial virus (RSV) is a serious pediatric pathogen of the lower respiratory tract worldwide. There is currently no clinically approved vaccine against RSV infection. Recently, it has been shown that a replication-deficient first generation adenoviral vector (FGAd), which encodes modified RSV attachment glycoprotein (G), elicits long-term protective immunity against RSV infection in mice. The major problem in developing such a vaccine is that G protein lacks MHC-I-restricted epitopes. However, RSV fusion glycoprotein (F) is a major cytotoxic T-lymphocyte epitope in humans and mice, therefore, an FGAd-encoding F (FGAd-F) was constructed and evaluated for its potential as an RSV vaccine in a murine model. Intranasal (i.n.) immunization with FGAd-F generated serum IgG, bronchoalveolar lavage secretory IgA, and RSV-specific CD8+ T-cell responses in BALB/c mice, with characteristic balanced or mixed Th1/Th2 CD4+ T-cell responses. Serum IgG was significantly elevated after boosting with i.n. FGAd-F. Upon challenge, i.n. immunization with FGAd-F displayed an effective protective role against RSV infection. These results demonstrate FGAd-F is able to induce effective protective immunity and is a promising vaccine regimen against RSV infection.

摘要

人呼吸道合胞病毒(RSV)是全球范围内引起小儿下呼吸道感染的一种严重病原体。目前尚无临床批准的针对RSV感染的疫苗。最近研究表明,一种编码修饰的RSV附着糖蛋白(G)的复制缺陷型第一代腺病毒载体(FGAd),可在小鼠体内引发针对RSV感染的长期保护性免疫。开发此类疫苗的主要问题在于G蛋白缺乏MHC-I限制性表位。然而,RSV融合糖蛋白(F)是人和小鼠体内主要的细胞毒性T淋巴细胞表位,因此构建了编码F的FGAd(FGAd-F),并在小鼠模型中评估其作为RSV疫苗的潜力。用FGAd-F进行鼻内(i.n.)免疫可在BALB/c小鼠中产生血清IgG、支气管肺泡灌洗分泌型IgA以及RSV特异性CD8+ T细胞应答,并伴有特征性的平衡或混合Th1/Th2 CD4+ T细胞应答。经鼻内FGAd-F加强免疫后,血清IgG显著升高。在受到RSV攻击时,用FGAd-F进行鼻内免疫对RSV感染显示出有效的保护作用。这些结果表明FGAd-F能够诱导有效的保护性免疫,是一种有前景的抗RSV感染疫苗方案。

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