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Immunogenicity and efficacy of a recombinant adenovirus expressing hemagglutinin from the H5N1 subtype of swine influenza virus in mice

机译:猪流感病毒H5N1亚型表达血凝素的重组腺病毒的免疫原性和功效

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摘要

The H5N1 influenza viruses infect a range of avian species and have recently been isolated from humans and pigs. In this study we generated a replication-defective recombinant adenovirus (rAd-H5HA-EGFP) expressing the hemagglutinin (HA) gene of H5N1 A/Swine/Fujian/1/2001 (SW/FJ/1/01) and evaluated its immunogenicity and protective efficacy in BALB/c mice. The recombinant virus induced high levels of hemagglutination inhibition (HI) antibody at a median tissue culture infective dose of 108 or 107. Compared with mice in the control groups, the mice vaccinated with rAd-H5HA-EGFP did not show apparent weight loss after challenge with either the homologous SW/FJ/1/01 or the heterologous H5N1 A/Chicken/Hunan/77/2005 (CK/HuN/77/05). Replication of the challenge virus was partially or completely inhibited, and viruses were detected at significantly lower numbers in the organs of the vaccinated mice, all of which survived the challenge with CK/HuN/77/05, whereas most of the control mice did not. These results indicate that rAd-H5HA-EGFP can provide effective immune protection from highly pathogenic H5N1 viruses in mice and is therefore a promising new candidate vaccine against H5N1 influenza in animals.
机译:H5N1流感病毒感染多种鸟类,最近已从人和猪中分离出来。在这项研究中,我们产生了表达H5N1 A /猪/福建/ 1/2001(SW / FJ / 1/01)的血凝素(HA)基因的复制缺陷型重组腺病毒(rAd-H5HA-EGFP),并评估了其免疫原性和在BALB / c小鼠中的保护作用。重组病毒以10 8 或10 7 的中等组织培养感染剂量诱导了高水平的血凝抑制(HI)抗体。与对照组小鼠相比,接种rAd-H5HA-EGFP的小鼠在用同源SW / FJ / 1/01或异源H5N1 A / Chicken / Hunan / 77/2005攻击后均未表现出明显的体重减轻( CK / HuN / 77/05)。攻击病毒的复制被部分或完全抑制,并且在接种小鼠的器官中检出的病毒数量明显减少,所有这些小鼠都在CK / HuN / 77/05的攻击下存活了下来,而大多数对照小鼠却没有。这些结果表明,rAd-H5HA-EGFP可以对小鼠中的高致病性H5N1病毒提供有效的免疫保护,因此是针对动物中H5N1流感的有希望的新候选疫苗。

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