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针对表达禽流感病毒血凝素抗原的重组鸡痘病毒载体疫苗的宿主反应特征分析。

Characterization of host responses against a recombinant fowlpox virus-vectored vaccine expressing the hemagglutinin antigen of an avian influenza virus.

作者信息

Hghihghi Hamid R, Read Leah R, Mohammadi Hakimeh, Pei Yanlong, Ursprung Claudia, Nagy Eva, Behboudi Shahriar, Haeryfar S M Mansour, Sharif Shayan

机构信息

Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada.

出版信息

Clin Vaccine Immunol. 2010 Mar;17(3):454-63. doi: 10.1128/CVI.00487-09. Epub 2010 Jan 13.

Abstract

There currently are commercial fowlpox virus (FPV)-vectored vaccines for use in chickens, including TROVAC-AIV H5, which expresses the hemagglutinin (HA) antigen of an avian influenza virus and can confer immunity against avian influenza in chickens. Despite the use of recombinant FPV (rFPV) for vaccine delivery, very little is known about the immune responses generated by these viruses in chickens. The present study was designed to investigate host responses to rFPV in vivo and in vitro. In cultured cells infected with TROVAC-AIV H5, there was an early increase in the expression of type I interferons (IFN), Toll-like receptors 3 and 7 (TLR3 and TLR7, respectively), TRIF, and MyD88, which was followed by a decrease in the expression of these genes at later time points. There also was an increase in the expression of interleukin-1beta (IL-1beta), IL-8, and beta-defensin genes at early time points postinfection. In chickens immunized with TROVAC-AIV H5, there was higher expression of IFN-gamma and IL-10 at day 5 postvaccination in spleen of vaccinated birds than in that of control birds. We further investigated the ability of the vaccine to induce immune responses against the HA antigen and discovered that there was a cell-mediated response elicited in vaccinated chickens against this antigen. The findings of this study demonstrate that FPV-vectored vaccines can elicit a repertoire of responses marked by the early expression of TLRs, type I interferons, and proinflammatory cytokines, as well as cytokines associated with adaptive immune responses. This study provides a platform for designing future generations of rFPV-vectored vaccines.

摘要

目前有用于鸡的商业禽痘病毒(FPV)载体疫苗,包括TROVAC-AIV H5,它表达禽流感病毒的血凝素(HA)抗原,可使鸡对禽流感产生免疫力。尽管使用重组FPV(rFPV)进行疫苗递送,但对于这些病毒在鸡体内产生的免疫反应知之甚少。本研究旨在调查宿主对rFPV的体内和体外反应。在用TROVAC-AIV H5感染的培养细胞中,I型干扰素(IFN)、Toll样受体3和7(分别为TLR3和TLR7)、TRIF和MyD88的表达早期增加,随后在后期时间点这些基因的表达下降。感染后早期时间点白细胞介素-1β(IL-1β)、IL-8和β-防御素基因的表达也增加。在用TROVAC-AIV H5免疫的鸡中,接种疫苗的鸡在接种后第5天脾脏中IFN-γ和IL-10的表达高于对照鸡。我们进一步研究了该疫苗诱导针对HA抗原的免疫反应的能力,发现接种疫苗的鸡对该抗原产生了细胞介导的反应。本研究结果表明,FPV载体疫苗可引发一系列反应,其特征为TLR、I型干扰素和促炎细胞因子以及与适应性免疫反应相关的细胞因子的早期表达。本研究为设计下一代rFPV载体疫苗提供了一个平台。

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