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基于副流感病毒 5 型(PIV5)的呼吸道合胞病毒(RSV)疫苗。

A respiratory syncytial virus (RSV) vaccine based on parainfluenza virus 5 (PIV5).

机构信息

Department of Infectious Diseases, University of Georgia, Athens, GA 30602, United States.

Department of Infectious Diseases, University of Georgia, Athens, GA 30602, United States; Intercollege Graduate Program in Cell and Developmental Biology, Pennsylvania State University, University Park, PA 16802, United States.

出版信息

Vaccine. 2014 May 23;32(25):3050-7. doi: 10.1016/j.vaccine.2014.03.049. Epub 2014 Apr 8.

Abstract

Human respiratory syncytial virus (RSV) is a leading cause of severe respiratory disease and hospitalizations in infants and young children. It also causes significant morbidity and mortality in elderly and immune compromised individuals. No licensed vaccine currently exists. Parainfluenza virus 5 (PIV5) is a paramyxovirus that causes no known human illness and has been used as a platform for vector-based vaccine development. To evaluate the efficacy of PIV5 as a RSV vaccine vector, we generated two recombinant PIV5 viruses - one expressing the fusion (F) protein and the other expressing the attachment glycoprotein (G) of RSV strain A2 (RSV A2). The vaccine strains were used separately for single-dose vaccinations in BALB/c mice. The results showed that both vaccines induced RSV antigen-specific antibody responses, with IgG2a/IgG1 ratios similar to those seen in wild-type RSV A2 infection. After challenging the vaccinated mice with RSV A2, histopathology of lung sections showed that the vaccines did not exacerbate lung lesions relative to RSV A2-immunized mice. Importantly, both F and G vaccines induced protective immunity. Therefore, PIV5 presents an attractive platform for vector-based vaccines against RSV infection.

摘要

人类呼吸道合胞病毒(RSV)是导致婴儿和幼儿严重呼吸道疾病和住院的主要原因。它也会导致老年人和免疫功能低下者出现重大发病率和死亡率。目前尚无许可疫苗。副流感病毒 5(PIV5)是一种副粘病毒,不会引起已知的人类疾病,已被用作基于载体的疫苗开发平台。为了评估 PIV5 作为 RSV 疫苗载体的功效,我们生成了两种重组 PIV5 病毒 - 一种表达融合(F)蛋白,另一种表达 RSV A2 株的附着糖蛋白(G)。疫苗株分别用于单次剂量接种 BALB/c 小鼠。结果表明,两种疫苗均诱导 RSV 抗原特异性抗体应答,IgG2a/IgG1 比值与野生型 RSV A2 感染相似。用 RSV A2 对接种疫苗的小鼠进行攻毒后,肺切片的组织病理学显示疫苗与 RSV A2 免疫的小鼠相比并未加重肺部病变。重要的是,F 和 G 疫苗均诱导了保护性免疫。因此,PIV5 为针对 RSV 感染的基于载体的疫苗提供了有吸引力的平台。

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