Rational design of an influenza-COVID-19 chimeric protective vaccine with HA-stalk and S-RBD

Li，Yulei1; Liu，Peipei2; Hao，Tianjiao3,4; Liu，Sheng5; Wang，Xi3,4; Xie，Yufeng6; Xu，Ke2; Lei，Wenwen2; Zhang，Cheng7; Han，Pu3; Li，Ying1; Jin，Xiyue8; Huan，Yu3,4; Lu，Yafei3,4; Zhang，Rong9; Li，Xiaoyan10; Zhao，Xin3; Xu，Kun11; Liao，Pu12; Lu，Xuancheng10; Bi，Yuhai3,4; Song，Hao4,11; Wu，Guizhen2; Zhu，Baoli3,4,13; Gao，George F.1,2,3,11

2023

10.1080/22221751.2023.2231573

Emerging Microbes and Infections   Impact Factor & Quartile

2222-1751

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.

broadly neutralizing antibody chimeric antigen influenza Omicron SARS-CoV-2 subunit vaccine Universal vaccine

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English

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National Key Research and Development Program of China[2021YFC2301300];National Natural Science Foundation of China[82122040];

WOS:001027250000001

2-s2.0-85164847338

Scopus

1.Savaid Medical School,University of Chinese Academy of Sciences,Beijing,China
2.NHC Key Laboratory of Biosafety,National Institute for Viral Disease Control and Prevention,Chinese Center for Disease Control and Prevention,Beijing,China
3.CAS Key Laboratory of Pathogen Microbiology and Immunology,Institute of Microbiology,Chinese Academy of Sciences,Beijing,China
4.University of Chinese Academy of Sciences,Beijing,China
5.Cryo-EM Center,Southern University of Science and Technology,Shenzhen,China
6.Department of Basic Medical Sciences,School of Medicine,Tsinghua University,Beijing,China
7.Xinjiang Key Laboratory of Biological Resources and Genetic Engineering,College of Life Science and Technology,Xinjiang University,Urumqi,China
8.School of Life Sciences,Division of Life Sciences and Medicine,University of Science and Technology of China,Hefei,China
9.State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources,Guangxi University,Nanning,China
10.Laboratory Animal Center,Chinese Center for Disease Control and Prevention (China CDC),Beijing,China
11.Research Network of Immunity and Health (RNIH),Beijing Institutes of Life Science,Chinese Academy of Sciences,Beijing,China
12.Department of Clinical Laboratory,Chongqing General Hospital,Chongqing,China
13.Department of Pathogenic Biology,School of Basic Medical Sciences,Southwest Medical University,Luzhou,China

Li，Yulei,Liu，Peipei,Hao，Tianjiao,et al. Rational design of an influenza-COVID-19 chimeric protective vaccine with HA-stalk and S-RBD[J]. Emerging Microbes and Infections,2023,12(2).

Li，Yulei.,Liu，Peipei.,Hao，Tianjiao.,Liu，Sheng.,Wang，Xi.,...&Gao，George F..(2023).Rational design of an influenza-COVID-19 chimeric protective vaccine with HA-stalk and S-RBD.Emerging Microbes and Infections,12(2).

Li，Yulei,et al."Rational design of an influenza-COVID-19 chimeric protective vaccine with HA-stalk and S-RBD".Emerging Microbes and Infections 12.2(2023).