Vaccination with Consensus H7 Elicits Broadly Reactive and Protective Antibodies against Eurasian and North American Lineage H7 Viruses
Gendeal M. Fadlallah,
Fuying Ma,
Zherui Zhang,
Mengchan Hao,
Juefu Hu,
Mingxin Li,
Haizhou Liu,
Biling Liang,
Yanfeng Yao,
Rui Gong,
Bo Zhang,
Di Liu,
Jianjun Chen
Affiliations
Gendeal M. Fadlallah
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
Fuying Ma
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
Zherui Zhang
CAS Key Laboratory of Special Pathogens and Biosafety, Chinese Academy of Sciences, Wuhan 430071, China
Mengchan Hao
CAS Key Laboratory of Special Pathogens and Biosafety, Chinese Academy of Sciences, Wuhan 430071, China
Juefu Hu
CAS Key Laboratory of Special Pathogens and Biosafety, Chinese Academy of Sciences, Wuhan 430071, China
Mingxin Li
CAS Key Laboratory of Special Pathogens and Biosafety, Chinese Academy of Sciences, Wuhan 430071, China
Haizhou Liu
CAS Key Laboratory of Special Pathogens and Biosafety, Chinese Academy of Sciences, Wuhan 430071, China
Biling Liang
CAS Key Laboratory of Special Pathogens and Biosafety, Chinese Academy of Sciences, Wuhan 430071, China
Yanfeng Yao
National Biosafety Laboratory, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China
Rui Gong
CAS Key Laboratory of Special Pathogens and Biosafety, Chinese Academy of Sciences, Wuhan 430071, China
Bo Zhang
CAS Key Laboratory of Special Pathogens and Biosafety, Chinese Academy of Sciences, Wuhan 430071, China
Di Liu
CAS Key Laboratory of Special Pathogens and Biosafety, Chinese Academy of Sciences, Wuhan 430071, China
Jianjun Chen
CAS Key Laboratory of Special Pathogens and Biosafety, Chinese Academy of Sciences, Wuhan 430071, China
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.
