Fadlallah Gendeal M, Ma Fuying, Zhang Zherui, Hao Mengchan, Hu Juefu, Li Mingxin, Liu Haizhou, Liang Biling, Yao Yanfeng, Gong Rui, Zhang Bo, Liu Di, Chen Jianjun
Department of Biotechnology, Key Laboratory of Molecular Biophysics of MOE, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China.
CAS Key Laboratory of Special Pathogens and Biosafety, Chinese Academy of Sciences, Wuhan 430071, China.
Vaccines (Basel). 2020 Mar 23;8(1):143. doi: 10.3390/vaccines8010143.
H7 subtype avian influenza viruses have caused outbreaks in poultry, and even human infection, for decades in both Eurasia and North America. Although effective vaccines offer the best protection against avian influenza viruses, antigenically distinct Eurasian and North American lineage subtype H7 viruses require the development of cross-protective vaccine candidates. In this study, a methodology called computationally optimized broadly reactive antigen (COBRA) was used to develop four consensus H7 antigens (CH7-22, CH7-24, CH7-26, and CH7-28). In vitro experiments confirmed the binding of monoclonal antibodies to the head and stem domains of cell surface-expressed consensus HAs, indicating display of their antigenicity. Immunization with DNA vaccines encoding the four antigens was evaluated in a mouse model. Broadly reactive antibodies against H7 viruses from Eurasian and North American lineages were elicited and detected by binding, inhibition, and neutralizing analyses. Further infection with Eurasian H7N9 and North American H7N3 virus strains confirmed that CH7-22 and CH7-24 conferred the most effective protection against hetero-lethal challenge. Our data showed that the consensus H7 vaccines elicit a broadly reactive, protective response against Eurasian and North American lineage H7 viruses, which are suitable for development against other zoonotic influenza viruses.
几十年来，H7亚型禽流感病毒在欧亚大陆和北美均引发了家禽疫情，甚至导致了人类感染。尽管有效的疫苗能提供针对禽流感病毒的最佳保护，但抗原性不同的欧亚和北美谱系H7亚型病毒需要研发具有交叉保护作用的候选疫苗。在本研究中，一种名为计算优化广谱反应性抗原（COBRA）的方法被用于开发四种共有H7抗原（CH7-22、CH7-24、CH7-26和CH7-28）。体外实验证实单克隆抗体与细胞表面表达的共有血凝素的头部和茎部结构域结合，表明其抗原性得以展示。在小鼠模型中评估了编码这四种抗原的DNA疫苗的免疫效果。通过结合、抑制和中和分析引发并检测到了针对欧亚和北美谱系H7病毒的广谱反应性抗体。进一步用欧亚H7N9和北美H7N3病毒株进行感染，证实CH7-22和CH7-24对异源致死性攻击提供了最有效的保护。我们的数据表明，共有H7疫苗引发了针对欧亚和北美谱系H7病毒的广谱反应性保护反应，适用于研发针对其他动物源性流感病毒的疫苗。
