Wang Xiang, Zhou Ping, Wu Mangteng, Yang Kaiyan, Guo Jingao, Wang Xuchen, Li Jun, Fang Zihao, Wang Guiqin, Xing Man, Zhou Dongming
Shanghai Public Health Clinical Center, Fudan University, Shanghai, 201508 China.
Vaccine Research Center, CAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, 200031 China.
NPJ Vaccines. 2020 Jul 9;5(1):57. doi: 10.1038/s41541-020-0206-5. eCollection 2020.
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.
由于流感病毒的高突变率和重组率，目前临床上获批的流感疫苗和抗流感药物对新出现的流感病毒流行提供的保护有限。因此，迫切需要高效的通用流感疫苗来确保人类安全与健康。流感广谱中和抗体的被动免疫可能成为控制流感感染的理想选择。从健康供体的外周血单核细胞中分离出的CR9114是一种靶向不同类型流感病毒的广谱中和单克隆抗体。由于腺病毒载体是最有前景的递送载体之一，我们采用黑猩猩腺病毒载体AdC68来表达CR9114作为通用抗流感疫苗，命名为AdC68-CR9114，并在动物模型中评估了其抗体表达以及广泛的预防和治疗效果。基于我们的研究结果，AdC68-CR9114感染的细胞在体外和体内均高水平表达广谱中和抗体，展现出生物学功能，并在不同时间点保护小鼠免受不同类型流感病毒的感染。本研究结果为控制和预防流感感染提供了一种新策略。
