Duan Yueqiang, Gu Hongjing, Chen Rui, Zhao Zhongpeng, Zhang Liangyan, Xing Li, Lai Chengcai, Zhang Peirui, Li Zhiwei, Zhang Keming, Wang Zhouhai, Zhang Shaogeng, Wang Xiliang, Yang Penghui
Beijing Institute of Microbiology and Epidemiology, State Key Laboratory of Pathogen and Biosecurity, Beijing, China.
Beijing Institute of Microbiology and Epidemiology, State Key Laboratory of Pathogen and Biosecurity, Beijing, China; Department of Pathogenic Biology and Medical Immunology, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, China.
PLoS One. 2014 Jun 17;9(6):e99322. doi: 10.1371/journal.pone.0099322. eCollection 2014.
In early spring 2013, the emergence of the influenza A (H7N9) virus in humans in Eastern China raised concerns of a new influenza pandemic. Development of a safe and effective H7N9 influenza vaccine is urgently needed. To this end, we first synthesized the hemagglutinin (HA) and neuraminidase (NA) genes of the influenza A (H7N9) virus A/AnHui/1/2013. Using reverse genetics, we rescued a reassortant virus (H7N9/PR8) that contained the HA and NA genes from wild-type H7N9 and six genes encoding internal proteins from the A/Puerto Rico/8/34 (PR8) virus. Next, the pathogenicity of the reassortant virus was evaluated both in vivo and in vitro. We found that the virus was non-pathogenic in mice and was stable after serial passaging in eggs. Furthermore, we found that a monovalent influenza A (H7N9) split vaccine prepared from the virus was immunogenic in mice and ferrets. When given intramuscularly, the vaccine (two doses of at least 15-µg) completely protected mice from normally lethal wild-type H7N9 virus challenge. In summary, our H7N9 vaccine, developed over a short time, is a potential candidate for further clinical evaluation and human use.
2013年早春,中国东部出现人感染甲型H7N9流感病毒的情况,引发了对一场新的流感大流行的担忧。迫切需要研发一种安全有效的H7N9流感疫苗。为此,我们首先合成了甲型H7N9流感病毒A/安徽/1/2013的血凝素(HA)和神经氨酸酶(NA)基因。利用反向遗传学技术,我们拯救出一种重配病毒(H7N9/PR8),它含有来自野生型H7N9的HA和NA基因以及来自A/波多黎各/8/34(PR8)病毒的六个编码内部蛋白的基因。接下来,对该重配病毒的致病性进行了体内和体外评估。我们发现该病毒在小鼠中无致病性,并且在鸡胚中连续传代后很稳定。此外,我们发现用该病毒制备的单价甲型H7N9流感裂解疫苗在小鼠和雪貂中具有免疫原性。肌肉注射时,该疫苗(两剂,每剂至少15微克)能完全保护小鼠免受通常致死剂量的野生型H7N9病毒攻击。总之,我们在短时间内研发出的H7N9疫苗是进一步进行临床评估和供人类使用的潜在候选疫苗。