Cell Academician Gao Fu of the Chinese Academy of Sciences and other teams have made important progress in the research of a new generation of new coronary pneumonia recombinant protein vaccine

Breakthrough infection of iNature SARS-CoV-2 variants becomes a global challenge for pandemic control
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Previously, the protein subunit vaccine ZF2001 was developed based on the dimeric receptor binding domain (RBD) of the prototype SARS-CoV-2
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On April 26, 2022, the team of Academician Gao Fu of the Institute of Microbiology, Chinese Academy of Sciences and the cooperative team published a research paper titled "Protective prototype-Beta and Delta-Omicron chimeric RBD-dimer vaccines against SARS-CoV-2" online in Cell.
This study developed a method for the design of a chimeric receptor binding domain (RBD) dimer protein vaccine that rapidly adapts to epidemic variants of COVID-19.
In contrast, chimeric RBD dimers can stimulate a broader spectrum of antibody responses and provide better protection in animals
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Mice and rhesus monkeys immunized with the prototype-Beta chimeric RBD dimer protein vaccine designed by this strategy showed protective effects against multiple mutant strains in challenge experiments.
The designed Delta-Omicron chimeric RBD dimerization The in vivo vaccine efficiently protects mice against Delta and Omicron infection and the resulting pneumonia
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The spike (S) protein on the surface of the new coronavirus is responsible for the receptor recognition and membrane fusion of the virus.
The RBD on the S protein is an important vaccine target, which stimulates the production of neutralizing antibodies and has the advantage of immunofocusing
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In the early stage, the team proposed the RBD dimer vaccine design concept of βcoronavirus S protein, and found that the neutralizing antibody titer in the serum of mice immunized with a dimer antigen designed by tandem repeating the RBD of the new coronavirus was higher than that of the monomer immunized effect (Dai et al, 2020, Cell)
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Based on this concept, the Institute of Microbiology, Chinese Academy of Sciences and Zhifei Biotechnology jointly developed the new coronary pneumonia recombinant protein vaccine ZF2001, which showed good safety and immunogenicity in Phase I/II clinical trials (Yang et al, 2021, Lancet Infectious Diseases), the results of phase III clinical trials showed that after three doses of ZF2001 inoculation, the protective efficacy of the vaccine against new coronary pneumonia of any severity in people aged 18 and over was 81.
43%, of which the protective efficacy for severe and above cases was 92.
87% %
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The vaccine was approved for emergency use in China and Uzbekistan in March 2021.
It is the first recombinant protein vaccine approved for use in the world.
It was also approved for emergency use in Indonesia and Colombia.
In addition, ZF2001 was approved in China this year.
Approved for marketing with conditions and as a sequential booster shot of the new crown inactivated vaccine
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Recombinant subunit protein vaccines have the advantages of high yield, high safety, easy storage and transportation, and are one of the important options for the prevention of new coronary pneumonia
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The pattern diagram of the article (pictured from Cell) The current situation of the new crown pneumonia epidemic is still very serious on a global scale.
New coronavirus variants are constantly emerging and popular, some of which will escape the antibody immune response of existing vaccines and cause breakthrough infections
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In particular, the Delta and Omicron variants swept the world in turn and became dominant epidemic strains, posing severe challenges to epidemic prevention and control
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Therefore, it is critical to develop a vaccine with broad-spectrum protection against mutants including Omicron
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Based on the design basis of the prototype strain homologous RBD dimer protein vaccine (ZF2001), the researchers developed a heterologous RBD dimer protein vaccine design method that can quickly adapt to the epidemic variant of the new crown.
The prototype-Beta chimeric protein vaccine has been verified in mice to induce a broader spectrum of antibody responses and protective effects than the homologous RBD dimers of prototype and Beta, and the prototype-Beta chimeric protein vaccine can immunize rhesus monkeys.
Provides protection against multiple strains of COVID-19
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Afterwards, the researchers designed a Delta-Omicron chimeric protein vaccine.
Compared with the prototype homologous RBD dimer vaccine, the immunized mice stimulated a broader spectrum of antibody responses, and challenged both Delta and Omicron variants.
Demonstrating better protective effect, these research data support the development of multivalent vaccines adapted to mutant strains to prevent circulating mutant strains.
This study provides great support for epidemic prevention and control in the context of the current epidemic of Omicron mutant strains
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Gao Fu, Academician of Beijing Institute of Biological Sciences and Institute of Microbiology, Chinese Academy of Sciences, Professor Wang Peiyi, Director of Cryo-EM Center, Southern University of Science and Technology, Researcher Dai Lianpan, Institute of Microbiology, Chinese Academy of Sciences, Researcher Peng Xiaozhong, Institute of Medical Biology, Chinese Academy of Medical Sciences, and Chief Biosafety Expert of Chinese Center for Disease Control and Prevention and Researcher Wu Guizhen, director of the BSL-3 Laboratory of the Institute for Viral Disease Control and Prevention, is the co-corresponding author
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Xu Kun, assistant researcher of Beijing Institute of Biological Sciences, Chinese Academy of Sciences, Gao Ping, doctoral student of Institute of Microbiology, Chinese Academy of Sciences, Liu Sheng, postdoctoral fellow of Cryo-EM Center, Southern University of Science and Technology, Professor Lu Shuaiyao, Institute of Medical Biology, Chinese Academy of Medical Sciences, Chinese Center for Disease Control and Prevention Lei Wenwen, an associate researcher at the Institute of Control, and Zheng Tianyi, a doctoral student at the School of Basic Medicine of Zhejiang University, are the co-first authors of the paper
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This project has been supported by the National Key R&D Program, the National Natural Science Foundation of China, the Strategic Pilot Project of the Chinese Academy of Sciences, the Bill & Melinda Gates Foundation, the China Postdoctoral Science Foundation, the Youth Promotion Association of the Chinese Academy of Sciences, the Shenzhen Science and Technology Innovation Committee Fund, Funded by the President of Southern University of Science and Technology, Zhuoyou Postdoctoral Fellow,
etc.

References: 1.
Dai, L.
, Zheng, T.
, Xu, K.
, Han, Y.
, Xu, L.
, Huang, E.
, An, Y.
, Cheng, Y.
, Li,S.
, Liu, M.
, et al.
(2020).
Auniversal design of betacoronavirus vaccines against COVID-19, MERS, and SARS.
Cell 182, 722-733 e711.
2.
Yang, S.
, Li, Y.
, Dai, L .
, Wang, J.
, He, P.
, Li, C.
, Fang, X.
, Wang, C.
, Zhao,X.
, Huang, E.
, et al.
(2021).
Safety and immunogenicity of a recombinant tandem -repeat dimeric RBD-based proteinsubunit vaccine (ZF2001) against COVID-19 in adults: two randomised, double-blind, placebo-controlled, phase 1 and 2 trials.
Lancet Infect Dis 21, 1107-1119.
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