A Chymotrypsin-Dependent Live-Attenuated Influenza Vaccine Provides Protective Immunity against Homologous and Heterologous Viruses
Peiqing He,
Mengxuan Gui,
Tian Chen,
Yue Zeng,
Congjie Chen,
Zhen Lu,
Ningshao Xia,
Guosong Wang,
Yixin Chen
Affiliations
Peiqing He
State Key Laboratory of Vaccines for Infectious Diseases, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, School of Public Health, Xiamen University, Xiamen 361102, China
Mengxuan Gui
State Key Laboratory of Vaccines for Infectious Diseases, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, School of Public Health, Xiamen University, Xiamen 361102, China
Tian Chen
State Key Laboratory of Vaccines for Infectious Diseases, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, School of Public Health, Xiamen University, Xiamen 361102, China
Yue Zeng
State Key Laboratory of Vaccines for Infectious Diseases, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, School of Public Health, Xiamen University, Xiamen 361102, China
Congjie Chen
State Key Laboratory of Vaccines for Infectious Diseases, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, School of Public Health, Xiamen University, Xiamen 361102, China
Zhen Lu
State Key Laboratory of Vaccines for Infectious Diseases, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, School of Public Health, Xiamen University, Xiamen 361102, China
Ningshao Xia
State Key Laboratory of Vaccines for Infectious Diseases, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, School of Public Health, Xiamen University, Xiamen 361102, China
Guosong Wang
State Key Laboratory of Vaccines for Infectious Diseases, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, School of Public Health, Xiamen University, Xiamen 361102, China
Yixin Chen
State Key Laboratory of Vaccines for Infectious Diseases, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, School of Public Health, Xiamen University, Xiamen 361102, China
Influenza virus is one of the main pathogens causing respiratory diseases in humans. Vaccines are the most effective ways to prevent viral diseases. However, the limited protective efficacy of current influenza vaccines highlights the importance of novel, safe, and effective universal influenza vaccines. With the progress of the COVID-19 pandemic, live-attenuated vaccines delivered through respiratory mucosa have shown robustly protective efficacy. How to obtain a safe and effective live-attenuated vaccine has become a major challenge. Herein, using the influenza virus as a model, we have established a strategy to quickly obtain a live-attenuated vaccine by mutating the cleavage site of the influenza virus. This mutated influenza virus can be specifically cleaved by chymotrypsin. It has similar biological characteristics to the original strain in vitro, but the safety is improved by at least 100 times in mice. It can effectively protect against lethal doses of both homologous H1N1 and heterologous H5N1 viruses post mucosal administration, confirming that the vaccine generated by this strategy has good safety and broad-spectrum protective activities. Therefore, this study can provide valuable insights for the development of attenuated vaccines for respiratory viruses or other viruses with cleavage sites.
