Virus-like particle vaccine by intranasal vaccination elicits protective immunity against respiratory syncytial viral infection in mice
Virus-like particle vaccine by intranasal vaccination elicits protective immunity against respiratory syncytial viral infection in mice
复制标题
通过鼻内接种的病毒样颗粒疫苗可引发小鼠针对呼吸道合胞病毒感染的保护性免疫力
DOI：
10.1093/abbs/gmw118
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发表时间：
2017-01-01
影响因子：
3.7
通讯作者：
Yang, Penghui
中科院分区：
文献类型：
--
作者：
Cai, Mengying;Wang, Cheng;Yang, Penghui
呼吸道合胞病毒(RSV)是婴儿和儿童下呼吸道感染的主要原因，但仍然没有获得许可的疫苗。在本报告中，我们开发了基于Bac-to-Bac杆状病毒表达系统的病毒样颗粒(VLP)疫苗，该疫苗由流感病毒基质(M1)蛋白和RSV融合蛋白(F)或糖蛋白(G)组成。用免疫印迹分析和电子显微镜对这些RSV VLP进行鉴定。BALB/c雌性小鼠鼻腔免疫(I.N.)对于RSV-F VLP和/或RSV-G VLP，显示出针对RSV的病毒特异性抗体应答。在RSV-F和RSV-G VLP混合感染的小鼠中，检测到总IgG、IgG1、IgG2a和粘膜IgA，显示出强大的细胞和粘膜免疫应答。此外，我们发现，这些混合RSV VLP增强了对活RSV攻击的保护，显示出显著减少了肺病毒复制，并明显减轻了与病毒感染相关的组织病理学变化。这些结果表明，RSV-F+RSV-G VLP鼻腔免疫是一种很有前途的候选疫苗，值得在棉花、大鼠和灵长类动物模型上进行进一步评估。
Respiratory syncytial virus (RSV) is a leading cause of lower respiratory infection in infants and children, but there is still no licensed vaccine available. In this report, we developed virus-like particle (VLP) vaccines based on the Bac-to-Bac baculovirus expression system, consisting of an influenza virus matrix (M1) protein and the RSV fusion protein (F) or glycoprotein (G). These RSV VLPs were identified by western blot analysis and electron microscopy. Female BALB/c mice immunized intranasally (i.n.) with RSV-F VLPs, RSV-G VLPs, or both showed viral-specific antibody responses against RSV. Total IgG, IgG1, IgG2a, and mucosal IgA were detected in mice with RSV-F plus RSV-G VLPs, revealing potent cellular and mucosal immune responses. Moreover, we found that these mixed RSV VLPs conferred enhanced protection against live RSV challenges, showing significant decreases in lung viral replication and obvious attenuation of histopathological changes associated with viral infections. These results demonstrate that RSV-F plus RSV-G VLPs by intranasal vaccination is a promising vaccine candidate that warrants further evaluation using cotton rat and primate models.