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Characterization of Host Responses against a Recombinant Fowlpox Virus-Vectored Vaccine Expressing the Hemagglutinin Antigen of an Avian Influenza Virus ▿

机译:宿主表达禽流感病毒血凝素抗原的重组鸡痘病毒载体疫苗反应的表征▿

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摘要

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-1β (IL-1β), IL-8, and beta-defensin genes at early time points postinfection. In chickens immunized with TROVAC-AIV H5, there was higher expression of IFN-γ 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.
机译:当前,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,并可以赋予鸡抵抗禽流感的免疫力。尽管使用重组FPV(rFPV)进行疫苗递送,但对于这些病毒在鸡中产生的免疫反应知之甚少。本研究旨在研究体内和体外宿主对rFPV的反应。在感染了TROVAC-AIV H5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的表达较早增加,其次是这些基因在以后的时间点表达减少。在感染后的早期时间点,白介素-1β(IL-1β),IL-8和β-防御素基因的表达也有所增加。在用TROVAC-AIV H5免疫的鸡中,接种疫苗的家禽的脾脏中IFN-γ和IL-10的表达比对照家禽的脾脏中的更高。我们进一步研究了疫苗诱导针对HA抗原的免疫反应的能力,并发现在接种疫苗的鸡中针对该抗原引起了细胞介导的反应。这项研究的结果表明,FPV载体疫苗可以引发以TLRs,I型干扰素和促炎性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为标志的反应。该研究为设计后代rFPV载体疫苗提供了平台。

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