Emerging Microbes and Infections (Dec 2023)
Rational design of an influenza-COVID-19 chimeric protective vaccine with HA-stalk and S-RBD
- Yulei Li,
- Peipei Liu,
- Tianjiao Hao,
- Sheng Liu,
- Xi Wang,
- Yufeng Xie,
- Ke Xu,
- Wenwen Lei,
- Cheng Zhang,
- Pu Han,
- Ying Li,
- Xiyue Jin,
- Yu Huan,
- Yafei Lu,
- Rong Zhang,
- Xiaoyan Li,
- Xin Zhao,
- Kun Xu,
- Pu Liao,
- Xuancheng Lu,
- Yuhai Bi,
- Hao Song,
- Guizhen Wu,
- Baoli Zhu,
- George F. Gao
Affiliations
- Yulei Li
- Savaid Medical School, University of Chinese Academy of Sciences, Beijing, People’s Republic of China
- Peipei Liu
- NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, People’s Republic of China
- Tianjiao Hao
- CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, People’s Republic of China
- Sheng Liu
- Cryo-EM Center, Southern University of Science and Technology, Shenzhen, People’s Republic of China
- Xi Wang
- CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, People’s Republic of China
- Yufeng Xie
- Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, People’s Republic of China
- Ke Xu
- NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, People’s Republic of China
- Wenwen Lei
- NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, People’s Republic of China
- Cheng Zhang
- Xinjiang Key Laboratory of Biological Resources and Genetic Engineering, College of Life Science and Technology, Xinjiang University, Urumqi, People’s Republic of China
- Pu Han
- CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, People’s Republic of China
- Ying Li
- Savaid Medical School, University of Chinese Academy of Sciences, Beijing, People’s Republic of China
- Xiyue Jin
- School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People’s Republic of China
- Yu Huan
- CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, People’s Republic of China
- Yafei Lu
- CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, People’s Republic of China
- Rong Zhang
- State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Guangxi University, Nanning, People’s Republic of China
- Xiaoyan Li
- Laboratory Animal Center, Chinese Center for Disease Control and Prevention (China CDC), Beijing, People’s Republic of China
- Xin Zhao
- CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, People’s Republic of China
- Kun Xu
- Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing, People’s Republic of China
- Pu Liao
- Department of Clinical Laboratory, Chongqing General Hospital, Chongqing, People’s Republic of China
- Xuancheng Lu
- Laboratory Animal Center, Chinese Center for Disease Control and Prevention (China CDC), Beijing, People’s Republic of China
- Yuhai Bi
- CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, People’s Republic of China
- Hao Song
- University of Chinese Academy of Sciences, Beijing, People’s Republic of China
- Guizhen Wu
- NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, People’s Republic of China
- Baoli Zhu
- CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, People’s Republic of China
- George F. Gao
- Savaid Medical School, University of Chinese Academy of Sciences, Beijing, People’s Republic of China
- DOI
- https://doi.org/10.1080/22221751.2023.2231573
- Journal volume & issue
-
Vol. 12,
no. 2
Abstract
Highly contagious respiratory illnesses like influenza and COVID-19 pose serious risks to public health. A two-in-one vaccine would be ideal to avoid multiple vaccinations for these diseases. Here, we generated a chimeric receptor binding domain of the spike protein (S-RBD) and hemagglutinin (HA)-stalk-based vaccine for both SARS-CoV-2 and influenza viruses. The S-RBD from SARS-CoV-2 Delta was fused to the headless HA from H1N1 (H1Delta), creating a chimera that forms trimers in solution. The cryo-electron microscopy structure of the chimeric protein complexed with the RBD-targeting CB6 and the HA-stalk-targeting CR9114 antibodies shows that the trimeric protein is stable and accessible for neutralizing antibody binding. Immunization with the vaccine elicited high and long-lasting neutralizing antibodies and effectively protected mice against the challenges of lethal H1N1 or heterosubtypic H5N8, as well as the SARS-CoV-2 Delta or Omicron BA.2 variants. Overall, this study offers a two-in-one universal vaccine design to combat infections caused by both SARS-CoV-2 variants of concern and influenza viruses.
Keywords
