表达甲型流感病毒血凝素的重组副流感病毒5型(PIV5)可使小鼠对甲型流感病毒攻击产生免疫力。

Recombinant parainfluenza virus 5 (PIV5) expressing the influenza A virus hemagglutinin provides immunity in mice to influenza A virus challenge.

作者信息

Tompkins S Mark, Lin Yuan, Leser George P, Kramer Kari A, Haas Debra L, Howerth Elizabeth W, Xu Jie, Kennett Mary J, Durbin Russell K, Durbin Joan E, Tripp Ralph, Lamb Robert A, He Biao

机构信息

Department of Infectious Diseases, University of Georgia, Athens, GA, USA.

出版信息

Virology. 2007 May 25;362(1):139-50. doi: 10.1016/j.virol.2006.12.005. Epub 2007 Jan 23.

Abstract

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 (HN) 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.

摘要

5型副流感病毒(PIV5),以前称为猴病毒5型(SV5),是一种不分节段的负链RNA病毒,作为疫苗载体具有几个优势。PIV5可感染多种细胞类型,几乎不产生细胞病变效应,在受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,PIV5可感染人类,但与任何已知的人类疾病无关。PIV5在包括Vero细胞在内的组织培养细胞中生长良好,Vero细胞已被批准用于疫苗生产,并且该病毒可以很容易地从培养基中获得。为了测试使用PIV5作为活疫苗载体的可行性,将甲型流感病毒A/Udorn/72(H3N2)株的血凝素(HA)基因作为额外基因插入到PIV5基因组中,位于血凝素神经氨酸酶(HN)基因和大(L)聚合酶基因之间。回收了含有乌栋(Udorn)HA基因的重组PIV5(rPIV5-H3),它在体外和体内的复制情况与野生型PIV5相似。rPIV5-H3感染的细胞表达的HA蛋白被整合到病毒粒子中,并且HA基因的添加并未增加病毒对小鼠的毒力。在6周龄的BALB/c小鼠中检测了rPIV5-H3作为活疫苗的效力。结果表明,单剂量接种可提供针对甲型流感病毒感染的广泛且可观的免疫力。

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