Efficient strategy for constructing duck enteritis virus-based live attenuated vaccine against homologous and heterologous H5N1 avian influenza virus and duck enteritis virus infection.

Efficient strategy for constructing duck enteritis virus-based live attenuated vaccine against homologous and heterologous H5N1 avian influenza virus and duck enteritis virus infection.
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DOI:
10.1186/s13567-015-0174-3
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发表时间:
2015-04-16
影响因子:
4.4
通讯作者:
Jin M
Jin M
中科院分区:
农林科学2区
文献类型:
--
作者:
Zou Z;Hu Y;Liu Z;Zhong W;Cao H;Chen H;Jin M

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鸭对鸭肝炎病毒、鸭肠炎病毒(DEV)、鸭坦布苏病毒(Tembusu virus)、尤其是H5 N1高致病性禽流感病毒(HPAIV)等多种病原体易感。由于鸭在H5 N1 HPAIV进化过程中的重要作用,通过疫苗免疫控制和根除鸭中的H5 N1 HPAIV被认为是最小化大流行爆发威胁的有效方法。因此,应该确定一种实用的策略来构建针对这些病原体的疫苗。在这项研究中,DEV作为一个候选的疫苗载体,提供血凝素(HA)基因的H5 N1,并评估其作为一个多价疫苗的潜力。将修饰的mini-F载体插入减毒DEV疫苗株C-KCE基因组的gB和UL 26基因连接处,以产生C-KCE的感染性细菌人工染色体(BAC)(vBAC-C-KCE)。通过交配辅助遗传整合克隆(MAGIC)技术将A/duck/Hubei/xn/2007(H5 N1)的HA基因插入到C-KCE基因组中,构建重组载体pBAC-C-KCE-HA。通过消除BAC骨架,开发了双价疫苗C-KCE-HA。用C-KCE-HA免疫鸭,诱导了针对H5的交叉反应性抗体和T细胞应答。此外,C-KCE-HA免疫的鸭提供了针对同源和异源HPAIV H5 N1和DEV临床体征、死亡和主要病毒复制的快速和持久的保护。总之,我们的BAC-C-KCE是一个有前途的平台,用于开发多价减毒活疫苗。本文的在线版本(doi:10.1186/s13567-015-0174-3)包含补充材料,可供授权用户使用。
Duck is susceptible to many pathogens, such as duck hepatitis virus, duck enteritis virus (DEV), duck tembusu virus, H5N1 highly pathogenic avian influenza virus (HPAIV) in particular. With the significant role of duck in the evolution of H5N1 HPAIV, control and eradication of H5N1 HPAIV in duck through vaccine immunization is considered an effective method in minimizing the threat of a pandemic outbreak. Consequently, a practical strategy to construct a vaccine against these pathogens should be determined. In this study, the DEV was examined as a candidate vaccine vector to deliver the hemagglutinin (HA) gene of H5N1, and its potential as a polyvalent vaccine was evaluated. A modified mini-F vector was inserted into the gB and UL26 gene junction of the attenuated DEV vaccine strain C-KCE genome to generate an infectious bacterial artificial chromosome (BAC) of C-KCE (vBAC-C-KCE). The HA gene of A/duck/Hubei/xn/2007 (H5N1) was inserted into the C-KCE genome via the mating-assisted genetically integrated cloning (MAGIC) to generate the recombinant vector pBAC-C-KCE-HA. A bivalent vaccine C-KCE-HA was developed by eliminating the BAC backbone. Ducks immunized with C-KCE-HA induced both the cross-reactive antibodies and T cell response against H5. Moreover, C-KCE-HA-immunized ducks provided rapid and long-lasting protection against homologous and heterologous HPAIV H5N1 and DEV clinical signs, death, and primary viral replication. In conclusion, our BAC-C-KCE is a promising platform for developing a polyvalent live attenuated vaccine. The online version of this article (doi:10.1186/s13567-015-0174-3) contains supplementary material, which is available to authorized users.
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