Recombinant parainfluenza virus 5 (PIV5) expressing the influenza A virus hemagglutinin provides immunity in mice to influenza A virus challenge
Recombinant parainfluenza virus 5 (PIV5) expressing the influenza A virus hemagglutinin provides immunity in mice to influenza A virus challenge
复制标题
DOI：
10.1016/j.virol.2006.12.005
复制
发表时间：
2007-05-25
期刊：
影响因子：
3.7
通讯作者：
He, Biao
中科院分区：
文献类型：
--
作者：
Tompkins, S. Mark;Lin, Yuan;He, Biao
副流感病毒5型（PIV 5），以前称为猿猴病毒5型（SV 5），是一种非节段负链RNA病毒，作为疫苗载体具有几个优点。PIV 5感染许多细胞类型，几乎不引起细胞病变效应，它在感染细胞的细胞质中复制，并且在其生命周期中没有DNA阶段，从而避免了将外源基因引入宿主DNA基因组的可能性。重要的是，PIV 5可以感染人类，但与任何已知的人类疾病无关。PIV 5在组织培养细胞中生长良好，包括已被批准用于疫苗生产的Vero细胞，并且病毒可以很容易地从培养基中获得。为了测试使用PIV 5作为活疫苗载体的可行性，将来自甲型流感病毒株A/Udorn/72（H3 N2）的血凝素（HA）基因插入到PIV 5基因组中，作为血凝素-神经氨酸酶（FIN）基因和大（L）聚合酶基因之间的额外基因。回收了含有Udorn HA基因的重组PIV 5（rPIV 5-H3），其体外和体内复制均与野生型PIV 5相似。rPIV 5-H3感染细胞表达的HA蛋白被整合到病毒体中，添加HA基因不会增加病毒在小鼠中的毒力。在6周龄BALB/c小鼠中检查rPIV 5-H3作为活疫苗的效力。结果表明，单剂量接种提供了广泛和相当大的免疫力，对甲型流感病毒感染。(C)2006爱思唯尔公司All rights reserved.
Parainfluenza virus type 5 (PIV5), formerly known as simian virus 5 (SV5), is a non-segmented negative strand RNA virus that offers several advantages as a vaccine vector. PIV5 infects many cell types causing little cytopathic effect, it replicates in the cytoplasm of infected cells, and does not have a DNA phase in its life cycle thus avoiding the possibility of introducing foreign genes into the host DNA genome. Importantly, PIV5 can infect humans but it is not associated with any known human illness. PIV5 grows well in tissue culture cells, including Vero cells, which have been approved for vaccine production, and the virus can be obtained easily from the media. To test the feasibility of using PIV5 as a live vaccine vector, the hemagglutinin (HA) gene from influenza A virus strain A/Udorn/72 (H3N2) was inserted into the PIV5 genome as an extra gene between the hemagglutinin-neuraminidase (FIN) gene and the large (L) polymerase gene. Recombinant PIV5 containing the HA gene of Udorn (rPIV5-H3) was recovered and it replicated similarly to wild type PIV5, both in vitro and in vivo. The HA protein expressed by rPIV5-H3-infected cells was incorporated into the virions and addition of the HA gene did not increase virus virulence in mice. The efficacy of rPIV5-H3 as a live vaccine was examined in 6-week-old BALB/c mice. The results show that a single dose inoculation provides broad and considerable immunity against influenza A virus infection. (C) 2006 Elsevier Inc. All rights reserved.