Adenovirus delivery of encoded monoclonal antibody protects against different types of influenza virus infection
Adenovirus delivery of encoded monoclonal antibody protects against different types of influenza virus infection
复制标题
腺病毒递送编码的单克隆抗体可预防不同类型的流感病毒感染
DOI：
10.1038/s41541-020-0206-5
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发表时间：
2020-07-09
期刊：
影响因子：
9.2
通讯作者：
Zhou, Dongming
中科院分区：
文献类型：
--
作者：
Wang, Xiang;Zhou, Ping;Zhou, Dongming
由于流感病毒的高变异率和重组率，目前获得临床许可的流感疫苗和抗流感药物对新出现的流感病毒疫情提供的保护有限。因此，迫切需要高效的通用流感疫苗来确保人类的安全和健康。被动接种流感广谱中和抗体可能成为控制流感感染的理想选择。从健康献血者的外周血单核细胞中分离出的CR9114是一种针对不同类型流感病毒的广谱中和单抗。鉴于腺病毒载体是最有前景的载体之一，我们利用黑猩猩腺病毒载体AdC68表达了CR9114作为一种通用的抗流感疫苗，命名为AdC68-CR9114，并在动物模型中评价了其抗体表达及其广泛的预防和治疗效果。根据我们的发现，AdC68-CR9114感染的细胞在体内外高水平表达广谱中和抗体，具有生物学功能，并在不同的时间点保护小鼠免受不同类型流感病毒的感染。这项研究的发现为控制和预防流感感染提供了新的战略。
Due to the high mutation and recombination rates of the influenza virus, current clinically licensed influenza vaccines and anti-influenza drugs provide limited protection against the emerging influenza virus epidemic. Therefore, universal influenza vaccines with high efficacy are urgently needed to ensure human safety and health. Passive immunization of influenza broadly neutralizing antibodies may become an ideal option for controlling influenza infection. CR9114 isolated from the peripheral blood mononuclear cells of healthy donors is a broadly neutralizing monoclonal antibody that targets different types of influenza viruses. As the adenovirus vector is one of the most promising delivery vehicles, we employed the chimpanzee adenoviral vector, AdC68, to express CR9114 as a universal anti-influenza vaccine, termed AdC68-CR9114, and evaluated its antibody expression and its broad spectrum of prophylactic and therapeutic effects in animal models. Based on our findings, AdC68-CR9114-infected cell expressed the broadly neutralizing antibody at a high level in vitro and in vivo, exhibited biological functions, and protected mice from different types of influenza virus infection at different time points. The findings from this study shed light on a new strategy for controlling and preventing influenza infection.