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

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)-st...

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Main Authors: 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
Format: Article
Language:English
Published: Taylor & Francis Group 2023-12-01
Series:Emerging Microbes and Infections
Subjects:
Online Access:https://www.tandfonline.com/doi/10.1080/22221751.2023.2231573
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author 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
author_facet 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
author_sort Yulei Li
collection DOAJ
description 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.
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spelling doaj.art-78b599e9f4e1408ba9f1981250f3f0882024-06-26T10:39:27ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512023-12-0112210.1080/22221751.2023.2231573Rational design of an influenza-COVID-19 chimeric protective vaccine with HA-stalk and S-RBDYulei Li0Peipei Liu1Tianjiao Hao2Sheng Liu3Xi Wang4Yufeng Xie5Ke Xu6Wenwen Lei7Cheng Zhang8Pu Han9Ying Li10Xiyue Jin11Yu Huan12Yafei Lu13Rong Zhang14Xiaoyan Li15Xin Zhao16Kun Xu17Pu Liao18Xuancheng Lu19Yuhai Bi20Hao Song21Guizhen Wu22Baoli Zhu23George F. Gao24Savaid Medical School, University of Chinese Academy of Sciences, Beijing, People’s Republic of ChinaNHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, People’s Republic of ChinaCAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, People’s Republic of ChinaCryo-EM Center, Southern University of Science and Technology, Shenzhen, People’s Republic of ChinaCAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, People’s Republic of ChinaDepartment of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, People’s Republic of ChinaNHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, People’s Republic of ChinaNHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, People’s Republic of ChinaXinjiang Key Laboratory of Biological Resources and Genetic Engineering, College of Life Science and Technology, Xinjiang University, Urumqi, People’s Republic of ChinaCAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, People’s Republic of ChinaSavaid Medical School, University of Chinese Academy of Sciences, Beijing, People’s Republic of ChinaSchool of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People’s Republic of ChinaCAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, People’s Republic of ChinaCAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, People’s Republic of ChinaState Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Guangxi University, Nanning, People’s Republic of ChinaLaboratory Animal Center, Chinese Center for Disease Control and Prevention (China CDC), Beijing, People’s Republic of ChinaCAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, People’s Republic of ChinaResearch Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing, People’s Republic of ChinaDepartment of Clinical Laboratory, Chongqing General Hospital, Chongqing, People’s Republic of ChinaLaboratory Animal Center, Chinese Center for Disease Control and Prevention (China CDC), Beijing, People’s Republic of ChinaCAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, People’s Republic of ChinaUniversity of Chinese Academy of Sciences, Beijing, People’s Republic of ChinaNHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, People’s Republic of ChinaCAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, People’s Republic of ChinaSavaid Medical School, University of Chinese Academy of Sciences, Beijing, People’s Republic of ChinaHighly 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.https://www.tandfonline.com/doi/10.1080/22221751.2023.2231573Universal vaccineSARS-CoV-2Omicroninfluenzasubunit vaccinechimeric antigen
spellingShingle 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
Rational design of an influenza-COVID-19 chimeric protective vaccine with HA-stalk and S-RBD
Emerging Microbes and Infections
Universal vaccine
SARS-CoV-2
Omicron
influenza
subunit vaccine
chimeric antigen
title Rational design of an influenza-COVID-19 chimeric protective vaccine with HA-stalk and S-RBD
title_full Rational design of an influenza-COVID-19 chimeric protective vaccine with HA-stalk and S-RBD
title_fullStr Rational design of an influenza-COVID-19 chimeric protective vaccine with HA-stalk and S-RBD
title_full_unstemmed Rational design of an influenza-COVID-19 chimeric protective vaccine with HA-stalk and S-RBD
title_short Rational design of an influenza-COVID-19 chimeric protective vaccine with HA-stalk and S-RBD
title_sort rational design of an influenza covid 19 chimeric protective vaccine with ha stalk and s rbd
topic Universal vaccine
SARS-CoV-2
Omicron
influenza
subunit vaccine
chimeric antigen
url https://www.tandfonline.com/doi/10.1080/22221751.2023.2231573
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