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《Cell，7月23日，A thermostable mRNA vaccine against COVID-19》

  • 来源专题：COVID-19科研动态监测
  • 编译者： zhangmin
  • 发布时间：2020-07-28

  • A thermostable mRNA vaccine against COVID-19

    Na-Na Zhang 6

    Xiao-Feng Li 6

    Yong-Qiang Deng 6

    You-Chun Wang

    Bo Ying

    Cheng-Feng Qin 7

    Published:July 23, 2020DOI:https://doi.org/10.1016/j.cell.2020.07.024

    Summary

    There has been an urgent need of vaccines against coronavirus disease 2019 (COVID-19) due to the ongoing SARS-CoV-2 pandemic. Among all approaches, messenger RNA (mRNA) -based vaccine has emerged as a rapid and versatile platform to quickly respond to such a challenge. Here, we developed a lipid-nanoparticle-encapsulated mRNA (mRNA-LNP) encoding the receptor binding domain (RBD) of SARS-CoV-2 as a vaccine candidate (termed ARCoV). Intramuscular immunization of ARCoV mRNA-LNPs elicited robust neutralizing antibodies against SARS-CoV-2 as well as Th1-biased cellular response in mice and non-human primates. Two doses of ARCoV immunization in mice conferred complete protection against the challenge of a SARS-CoV-2 mouse adapted strain. Additionally, ARCoV was manufactured in liquid formulation and can be stored at room temperature for at least one week. This novel COVID-19 mRNA vaccine, ARCoV, is currently being evaluated in phase 1 clinical trials.

  • 原文来源：https://www.cell.com/cell/fulltext/S0092-8674(20)30932-6
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  • 《Cell，6月28日，A universal design of betacoronavirus vaccines against COVID-19, MERS and SARS》
    • 来源专题：COVID-19科研动态监测
    • 编译者：zhangmin
    • 发布时间：2020-06-29
    • A universal design of betacoronavirus vaccines against COVID-19, MERS and SARS Lianpan Dai 12 Tianyi Zheng 12 Kun Xu 12 Chuan Qin Jinghua Yan George F. Gao 13 Show all authors Show footnotes Published:June 28, 2020DOI:https://doi.org/10.1016/j.cell.2020.06.035 Summary Vaccines are urgently needed to control the ongoing pandemic COVID-19 and previously-emerging MERS/SARS caused by coronavirus (CoV) infections. The CoV spike receptor-binding domain (RBD) is an attractive vaccine target but is undermined by limited immunogenicity. We describe a dimeric form of MERS-CoV RBD that overcomes this limitation. The RBD-dimer significantly increased neutralizing antibody (NAb) titers compared to conventional monomeric form and protected mice against MERS-CoV infection. Crystal structure showed RBD-dimer fully exposed dual receptor-binding motifs, the major target for NAbs. Structure-guided design further yielded a stable version of RBD-dimer as a tandem repeat single-chain (RBD-sc-dimer) which retained the vaccine potency. We generalized this strategy to design vaccines against COVID-19 and SARS, achieving 10-100-fold enhancement of NAb titers. RBD-sc-dimers in pilot scale production yielded high yields, supporting their scalability for further clinical development. The framework of immunogen design can be universally applied to other beta-CoV vaccines to counter emerging threats.
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