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    Home > Active Ingredient News > Infection > Zhu Fengcai/Wang Xiangxi/Qin Chengfeng collaborated to reverse design and develop a new generation of new coronavirus genetically engineered vaccines based on the immune characteristics of neutralizing antibodies

    Zhu Fengcai/Wang Xiangxi/Qin Chengfeng collaborated to reverse design and develop a new generation of new coronavirus genetically engineered vaccines based on the immune characteristics of neutralizing antibodies

    • Last Update: 2021-04-14
    • Source: Internet
    • Author: User
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    On March 27, 2021, the team of Professor Fengcai Zhu from the Jiangsu Centers for Disease Control and Prevention, the team of Researcher Wang Xiangxi of the Institute of Biophysics of the Chinese Academy of Sciences, and the team of Researcher Qin Chengfeng of the Military Medical College, etc.
    , published A proof of concept for neutralizing antibody-guided online in the National Science Review Research paper on vaccine design against SARS-CoV-2.

    This study conducted an in-depth analysis of the binding sites and mechanism of action of the two key domains of the new coronavirus Spike (S) protein, RBD and NTD, and their corresponding fully human neutralizing antibodies FC08 and FC05, and proposed neutralizing antibodies.
    The concept of "Cocktail" designed the conceptual design of a new generation genetically engineered vaccine against the S protein RBD and NTD two-component subunit of the new coronavirus and completed the functional verification.

    This is after Wang Xiangxi's research group participated in the research and development of new coronavirus inactivated vaccines (Gao Q, et, al Science 2020a; Zhang Y, et, al Lancet Infectious Diseases 2020a), and the new coronavirus neutralizing antibody systemic study (Lv Z, et, al Science 2020b; Zhu L, et.
    al NSR 2020; Yao H, et.
    al Cell Res 2020a; Wang N, et al, Cell Res 2020b; Sun Y, et.
    al Cell Res 2021a), based on the immune characteristics of neutralizing antibodies Another in-depth research result of reverse design immunogen.

    The neutralizing antibodies FC08 and FC05 in this study were screened by Fengcai Zhu's team.
    They were sorted and cloned from the peripheral blood of the new coronavirus super spreader during the recovery period.Among them, the NTD-targeting mAb FC05 and the RBD domain-targeting mAb FC08 can effectively neutralize the new coronavirus at the sub-nM level.

    FC05 and FC08 were applied to the design concept of neutralizing antibody "Cocktail", aiming to target epitopes in different domains of S protein to achieve a more efficient neutralization effect (Yao H, et.
    al Cell Res 2020a; Wang N, et al, Cell Res 2020b; Sun Y, et.
    al Cell Res 2021).

    The neutralization effect of FC08 and FC05 antibodies has also been verified in cell experiments and animal models, and it is found that the neutralization ability has reached a synergistic effect of 1+1>2.

    Based on the structural analysis of cryo-electron microscopy, the joint research team designed the RBD and NTD two-component subunit COVID-19 vaccine.
    Experiments in rabbits and rhesus monkeys verified that the level of neutralizing antibodies induced by the vaccine was significantly higher than that of the first-generation COVID-19 vaccine.

    The two-shot immunization of rhesus monkeys produced complete protection against the new coronavirus attack, and there was no antibody-dependent enhancement phenomenon.

    Compared with S-trimeric protein or S1 subunit vaccines, two-component vaccines have three advantages: 1) Simple process, high yield, and significantly improved productivity; 2) Enrichment and amplification of key antigen epitope information, namely: Contains The key neutralization site area and reduce the non-neutralization site area; 3) Optimize the ratio of immune two-component antigens to produce a variety of neutralizing antibodies with balanced abundance.

    This paper was published online in the preprint version on September 5, 2020.

    After the first generation of the new coronavirus vaccine mRNA-1273 designed with the S protein target by Moderna in the United States was used urgently, the next-generation mRNA-1283 developed in 2021 also turned to the design ideas of RBD and NTD, supporting the cutting-edge and cutting-edge of the design ideas.
    scientific.

    In May 2020, Zhu Fengcai's team and others signed a strategic cooperation agreement on the joint development of new crown vaccine research and development with Ruike Biotechnology and Taizhou Pharmaceutical High-tech Industrial Park Management Committee, and initiated the research and development of a recombinant two-component new crown vaccine project in Jiangsu Province.
    , Will enter the first phase of clinical trials in the near future. The vaccine design concept based on antigen and antibody structure proposed in this research points out the direction for new crown drug development and vaccine research and development.

    Antigen target design is the cornerstone of the innovative concept of Trinity vaccine research and development.
    The ideal antigen target design should include as many neutralization sites as possible and reduce non-neutralization sites, which can improve the immune effect of the vaccine while reducing the safety of immunopathological reactions.
    Sexual risk.

    This design concept promotes the upgrading of vaccine research and development in my country, and makes a leading contribution for my country's new generation of independent innovative vaccines to enter the forefront of the world.

    Wang Xiangxi's research group, Institute of Biophysics, Chinese Academy of Sciences ( is a long-term recruitment of postdoctoral fellows.

    Related reading: 1.
    ScienceThe Chinese team released the results of the first animal experiment of the new coronavirus vaccine: the new coronavirus inactivated vaccine is safe and effective in the rhesus monkey model 2.
    CHOM | You Fuping/Wang Xiangxi/Qin Chuan cooperate to reveal the induction of new coronavirus infection Anti-bacterial innate immune response mechanism and discovery of new potential therapeutic targets 3.
    Cell Research | You Fuping/Wang Xiangxi collaborated to reveal that the new coronavirus S protein directly binds and activates TLR4 to induce anti-bacterial innate immunity and viral sepsis 4.
    Double The lock-in mechanism helps the new coronavirus therapeutic antibody to enter clinical research.
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