Protective prototype-Beta and Delta-Omicron chimeric RBD-dimer vaccines against SARS-CoV-2

Kun Xu; Ping Gao; Sheng Liu; Shuaiyao Lu; Wenwen Lei; Tianyi Zheng; Xueyuan Liu; Yufeng Xie; Zhennan Zhao; Shuxin Guo; Cong Tang; Yun Yang; Wenhai Yu; Junbin Wang; Yanan Zhou; Qing Huang; Chuanyu Liu; Yaling An; Rong Zhang; Yuxuan Han; Minrun Duan; Shaofeng Wang; Chenxi Yang; Changwei Wu; Xiaoya Liu; Guangbiao She; Yan Liu; Xin Zhao; Ke Xu; Jianxun Qi; Guizhen Wu; Xiaozhong Peng; Lianpan Dai; Peiyi Wang; George F Gao

doi:10.1016/j.cell.2022.04.029

Protective prototype-Beta and Delta-Omicron chimeric RBD-dimer vaccines against SARS-CoV-2

Cell. 2022 Jun 23;185(13):2265-2278.e14. doi: 10.1016/j.cell.2022.04.029. Epub 2022 Apr 27.

Authors

Kun Xu¹, Ping Gao², Sheng Liu³, Shuaiyao Lu⁴, Wenwen Lei⁵, Tianyi Zheng⁶, Xueyuan Liu⁷, Yufeng Xie⁸, Zhennan Zhao², Shuxin Guo⁹, Cong Tang⁴, Yun Yang⁴, Wenhai Yu⁴, Junbin Wang⁴, Yanan Zhou⁴, Qing Huang⁴, Chuanyu Liu¹⁰, Yaling An¹¹, Rong Zhang¹⁰, Yuxuan Han¹¹, Minrun Duan¹², Shaofeng Wang², Chenxi Yang², Changwei Wu¹³, Xiaoya Liu¹³, Guangbiao She¹³, Yan Liu¹⁴, Xin Zhao¹⁵, Ke Xu⁵, Jianxun Qi¹⁵, Guizhen Wu¹⁶, Xiaozhong Peng¹⁷, Lianpan Dai¹⁸, Peiyi Wang¹⁹, George F Gao²⁰

Affiliations

¹ Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, China.
² CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
³ Cryo-EM Center, Southern University of Science and Technology, Shenzhen 518055, China.
⁴ National Kunming High-level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming 650031, China.
⁵ NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China.
⁶ Zhejiang University School of Medicine, Hangzhou 310058, China.
⁷ School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan 250012, China.
⁸ Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China.
⁹ Faculty of Health Sciences, University of Macau, Macau, SAR 999078, China.
¹⁰ State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Guangxi University, Nanning 530004, China.
¹¹ Savaid Medical School, University of Chinese Academy of Sciences, Beijing 101408, China.
¹² School of Life Sciences, Yunnan University, Kunming 650091, China.
¹³ Anhui Zhifei Longcom Biopharmaceutical Co. Ltd, Hefei 230088, China.
¹⁴ Chongqing Medleader Bio-Pharm, Chongqing 401338, China.
¹⁵ CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
¹⁶ NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China. Electronic address: wugz@ivdc.chinacdc.cn.
¹⁷ National Kunming High-level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming 650031, China; State Key Laboratory of Medical Molecular Biology, Department of Molecular Biology and Biochemistry, Institute of Basic Medical Sciences, Medical Primate Research Center, Neuroscience Center, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing 100005, China. Electronic address: pengxiaozhong@pumc.edu.cn.
¹⁸ CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address: dailp@im.ac.cn.
¹⁹ Cryo-EM Center, Southern University of Science and Technology, Shenzhen 518055, China. Electronic address: wangpy@sustech.edu.cn.
²⁰ Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, China; CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China; Savaid Medical School, University of Chinese Academy of Sciences, Beijing 101408, China. Electronic address: gaof@im.ac.cn.

Abstract

Breakthrough infections by SARS-CoV-2 variants become the global challenge for pandemic control. Previously, we developed the protein subunit vaccine ZF2001 based on the dimeric receptor-binding domain (RBD) of prototype SARS-CoV-2. Here, we developed a chimeric RBD-dimer vaccine approach to adapt SARS-CoV-2 variants. A prototype-Beta chimeric RBD-dimer was first designed to adapt the resistant Beta variant. Compared with its homotypic forms, the chimeric vaccine elicited broader sera neutralization of variants and conferred better protection in mice. The protection of the chimeric vaccine was further verified in macaques. This approach was generalized to develop Delta-Omicron chimeric RBD-dimer to adapt the currently prevalent variants. Again, the chimeric vaccine elicited broader sera neutralization of SARS-CoV-2 variants and conferred better protection against challenge by either Delta or Omicron SARS-CoV-2 in mice. The chimeric approach is applicable for rapid updating of immunogens, and our data supported the use of variant-adapted multivalent vaccine against circulating and emerging variants.

Keywords: COVID19 vaccine; Delta variant; Omicron variant; RBD; SARS-CoV-2; VOC; immunogen structure; receptor-binding domain; vaccine protection; variant of concern.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antibodies, Neutralizing
Antibodies, Viral
COVID-19 Vaccines
COVID-19* / prevention & control
Humans
Mice
SARS-CoV-2 / genetics
Vaccines*

Substances

Antibodies, Neutralizing
Antibodies, Viral
COVID-19 Vaccines
Vaccines

Supplementary concepts

SARS-CoV-2 variants