Both haemagglutinin-specific antibody and T cell responses induced by a chimpanzee adenoviral vaccine confer protection against influenza H7N9 viral challenge

Both haemagglutinin-specific antibody and T cell responses induced by a chimpanzee adenoviral vaccine confer protection against influenza H7N9 viral challenge
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黑猩猩腺病毒疫苗诱导的血凝素特异性抗体和 T 细胞反应均可提供针对 H7N9 流感病毒攻击的保护作用

DOI:
10.1038/s41598-017-02019-1
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发表时间:
2017-05
期刊:
影响因子:
4.6
通讯作者:
Dongming Dongming
Dongming Dongming
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Xiang Wang;Weihui Fu;Songhua Yuan;Xi Yang;Yufeng Song;Lulu Liu;Yudan Chi;Tao Cheng;Man Xing;Yan Zhang;Chao Zhang;Yong Yang;Caihong Zhu;Xiaoyan Zhang;Sidong Xiong;Jianqing Xu;Dongming Dongming

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自2013年以来,中国爆发或散发的新型H7N9流感病毒已导致数百人死亡和数千人患病。迫切需要H7N9疫苗,因为目前还没有获得许可的针对H7N9流感的人用疫苗。在这里,我们开发了一种重组腺病毒为基础的疫苗,AdC 68-H7 HA,通过克隆H7N9血凝素(HA)基因到黑猩猩腺病毒载体AdC 68。在小鼠以及豚鼠中评估AdC 68-H7 HA的功效。为了比较,还产生了基于HA的H7N9 DNA疫苗,并在小鼠和豚鼠中进行了测试。结果表明,AdC 68-H7 HA和DNA疫苗初免-腺病毒加强方案在动物中诱导了有效的免疫应答,并完全保护小鼠免受致死性H7N9流感病毒攻击。免疫后血清转移实验表明,抗体应答可以完全保护免受致死性攻击,而T细胞耗竭实验表明HA特异性CD 8 +T细胞应答也有助于保护。因此,HA特异性体液免疫和细胞免疫在保护中起重要作用。这些数据表明,表达HA的黑猩猩腺病毒是H7N9病毒或其他流感病毒亚型的有希望的疫苗候选者。
Since 2013, the outbreak or sporadic infection of a new reassortant H7N9 influenza virus in China has resulted in hundreds of deaths and thousands of illnesses. An H7N9 vaccine is urgently needed, as a licensed human vaccine against H7N9 influenza is currently not available. Here, we developed a recombinant adenovirus-based vaccine, AdC68-H7HA, by cloning the H7N9 haemagglutinin (HA) gene into the chimpanzee adenoviral vector AdC68. The efficacy of AdC68-H7HA was evaluated in mice as well as guinea pigs. For comparison, an H7N9 DNA vaccine based on HA was also generated and tested in mice and guinea pigs. The results demonstrated that both AdC68-H7HA and the DNA vaccine prime-adenovirus boost regimen induced potent immune responses in animals and completely protected mice from lethal H7N9 influenza viral challenge. A post-immunization serum transfer experiment showed that antibody responses could completely protect against lethal challenge, while a T cell depletion experiment indicated that HA-specific CD8+T cells responses also contributed to protection. Therefore, both HA-specific humoral immunity and cellular immunity play important roles in the protection. These data suggest that the chimpanzee adenovirus expressing HA is a promising vaccine candidate for H7N9 virus or other influenza viral subtypes.
过去、现在和未来可能的人类感染甲型流感病毒 H7 亚型。
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