Chimpanzee adenovirus vector-based avian influenza vaccine completely protects mice against lethal challenge of H5N1
Chimpanzee adenovirus vector-based avian influenza vaccine completely protects mice against lethal challenge of H5N1
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DOI：
10.1016/j.vaccine.2016.08.066
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发表时间：
2016-09-22
期刊：
影响因子：
5.5
通讯作者：
Zhou, Dongming
中科院分区：
文献类型：
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作者：
Cheng, Tao;Wang, Xiang;Zhou, Dongming
高致病性H5N1禽流感病毒由于其基因组的重组和突变，可能引起下一次流感大流行。针对这种病毒的疫苗对于应对其潜在威胁很重要。黑猩猩腺病毒（Ad）载体是一种新型的疫苗载体，它具有人类血清型Ad载体的优点，但不受人类预先存在的针对疫苗载体的中和抗体的影响。基于复制缺陷黑猩猩Ad载体AdC7，我们产生了一种新的H5N1候选疫苗AdC7- h5ha，它表达H5N1血凝素（HA）。在小鼠试验中，该疫苗显著减少了病毒载量和肺组织中的病理病变，并完全保护小鼠免受同源病毒的致命攻击。在机制上，AdC7-H5HA疫苗可以在小鼠中诱导ha特异性体液和细胞介导的免疫反应。此外，血清转移实验表明，单独中和抗体可以提供保护。总之，我们的研究结果表明，表达流感病毒HA的黑猩猩Ad载体可能是H5N1病毒和其他流感病毒亚型的有希望的候选疫苗。(C) 2016 Elsevier Ltd.版权所有。
Highly pathogenic avian H5N1 viruses may give rise to the next influenza pandemic due to their reassortment and mutation of the genome. Vaccine against this virus is important for coping with its potential threat. Chimpanzee adenovirus (Ad) vectors are a novel type of vaccine vectors that share the advantages of human serotype Ad vectors but without being affected by pre-existing human neutralizing antibody to the vaccine vector. Based on a replication-deficient chimpanzee Ad vector, AdC7, we generated a novel H5N1 vaccine candidate AdC7-H5HA that expresses H5N1 Hemagglutinin (HA). When tested in mice, the vaccine significantly reduced the virus load and pathological lesions in the lung tissues, and conferred complete protection against lethal challenge by a homologous virus. Mechanistically, the AdC7-H5HA vaccine can induce both HA-specific humoral and cell-mediated immune responses in mice. Also, sera transfer experiments demonstrated that neutralizing antibodies alone could provide protection. In conclusion, our results show that chimpanzee Ad vector expressing influenza virus HA may represent a promising vaccine candidate for H5N1 viruses and other influenza virus subtypes. (C) 2016 Elsevier Ltd. All rights reserved.