System Maintenance Notice

Please note that maintenance work is scheduled between 4 AM and 5 AM - CET. During this time, you may experience reduced performance. Thanks for your patience.

Publications

Journal Article Ppublish 22 citations

PubMed: 36323313 DOI: 10.1016/j.chom.2022.10.011

Lineage-mosaic and mutation-patched spike proteins for broad-spectrum COVID-19 vaccine.

Cell Host Microbe 30(12):1732-1744.e7

Authors: Yangtao Wu, Shaojuan Wang, Yali Zhang, Lunzhi Yuan, Qingbing Zheng, Min Wei, Yang Shi, Zikang Wang, Jian Ma, Kai Wang, Meifeng Nie, Jin Xiao, Zehong Huang, Peiwen Chen, Huilin Guo, Miaolin Lan, Jingjing Xu, Wangheng Hou, Yunda Hong, Dabing Chen, Hui Sun, Hualong Xiong, Ming Zhou, Che Liu, Wenjie Guo, Huiyu Guo, Jiahua Gao, Congling Gan, Zhixiong Li, Haitao Zhang, Xinrui Wang, Shaowei Li, Tong Cheng, Qinjian Zhao, Yixin Chen, Ting Wu, Tianying Zhang, Jun Zhang, Hua Cao, Huachen Zhu, Quan Yuan, Yi Guan, Ningshao Xia

Affiliations

  • State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health & School of Life Sciences, Xiamen University, Xiamen 361102, China.
  • State Key Laboratory of Emerging Infectious Diseases, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China; Guangdong-Hong Kong Joint Laboratory of Emerging Infectious Diseases, Joint Laboratory for International Collaboration in Virology and Emerging Infectious Diseases, Joint Institute of Virology (STU/HKU), Shantou University, Shantou, Guangdong 515063, China; EKIH Pathogen Research Institute, Futian District, Shenzhen, Guangdong 518045, China.
  • Key Laboratory of Technical Evaluation of Fertility Regulation for Non-human Primate, National Health Commission, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350013, China.
  • State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health & School of Life Sciences, Xiamen University, Xiamen 361102, China.
  • State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health & School of Life Sciences, Xiamen University, Xiamen 361102, China.
  • Key Laboratory of Technical Evaluation of Fertility Regulation for Non-human Primate, National Health Commission, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350013, China.
  • State Key Laboratory of Emerging Infectious Diseases, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China; Guangdong-Hong Kong Joint Laboratory of Emerging Infectious Diseases, Joint Laboratory for International Collaboration in Virology and Emerging Infectious Diseases, Joint Institute of Virology (STU/HKU), Shantou University, Shantou, Guangdong 515063, China; EKIH Pathogen Research Institute, Futian District, Shenzhen, Guangdong 518045, China.
  • State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health & School of Life Sciences, Xiamen University, Xiamen 361102, China.
  • State Key Laboratory of Emerging Infectious Diseases, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China; Guangdong-Hong Kong Joint Laboratory of Emerging Infectious Diseases, Joint Laboratory for International Collaboration in Virology and Emerging Infectious Diseases, Joint Institute of Virology (STU/HKU), Shantou University, Shantou, Guangdong 515063, China; EKIH Pathogen Research Institute, Futian District, Shenzhen, Guangdong 518045, China.
  • State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health & School of Life Sciences, Xiamen University, Xiamen 361102, China; Research Unit of Frontier Technology of Structural Vaccinology, Chinese Academy of Medical Sciences, Xiamen, Fujian 361102, China.

Abstract

SARS-CoV-2 spread in humans results in continuous emergence of new variants, highlighting the need for vaccines with broad-spectrum antigenic coverage. Using inter-lineage chimera and mutation-patch strategies, we engineered a recombinant monomeric spike variant (STFK1628x) that contains key regions and residues across multiple SAR-CoV-2 variants. STFK1628x demonstrated high immunogenicity and mutually complementary antigenicity to its prototypic form (STFK). In hamsters, a bivalent vaccine composed of STFK and STFK1628x elicited high titers of broad-spectrum neutralizing antibodies to 19 circulating SARS-CoV-2 variants, including Omicron sublineages BA.1, BA.1.1, BA.2, BA.2.12.1, BA.2.75, and BA.4/5. Furthermore, this vaccine conferred robust protection against intranasal challenges by either SARS-CoV-2 ancestral strain or immune-evasive Beta and Omicron BA.1. Strikingly, vaccination with the bivalent vaccine in hamsters effectively blocked within-cage virus transmission of ancestral SARS-CoV-2, Beta variant, and Omicron BA.1 to unvaccinated sentinels. Thus, our study provided insight and antigen candidates for the development of next-generation COVID-19 vaccines.

MeSH

Vaccines, Covid-19 Vaccines, Host-Parasite Interactions, Covid-19, Mutation

Cited by