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A lung-selective delivery of mRNA encoding broadly neutralizing antibody against SARS-CoV-2 infection

Author

Listed:
  • Wanbo Tai

    (Tsinghua University
    Shenzhen Bay Laboratory)

  • Kai Yang

    (Tsinghua University)

  • Yubin Liu

    (Tsinghua University)

  • Ruofan Li

    (Tsinghua University)

  • Shengyong Feng

    (Tsinghua University)

  • Benjie Chai

    (Tsinghua University)

  • Xinyu Zhuang

    (Chinese Academy of Agricultural Sciences)

  • Shaolong Qi

    (Tsinghua University)

  • Huicheng Shi

    (Tsinghua University)

  • Zhida Liu

    (Shanxi Academy of Advanced Research and Innovation)

  • Jiaqi Lei

    (Tsinghua University)

  • Enhao Ma

    (Tsinghua University)

  • Weixiao Wang

    (Tsinghua University
    Shenzhen Bay Laboratory)

  • Chongyu Tian

    (Tsinghua University
    Shenzhen Bay Laboratory)

  • Ting Le

    (Tsinghua University
    Shenzhen Bay Laboratory)

  • Jinyong Wang

    (Shenzhen Bay Laboratory)

  • Yunfeng Chen

    (Shenzhen Bay Laboratory)

  • Mingyao Tian

    (Chinese Academy of Agricultural Sciences)

  • Ye Xiang

    (Tsinghua University)

  • Guocan Yu

    (Tsinghua University)

  • Gong Cheng

    (Tsinghua University
    Tsinghua University)

Abstract

The respiratory system, especially the lung, is the key site of pathological injury induced by SARS-CoV-2 infection. Given the low feasibility of targeted delivery of antibodies into the lungs by intravenous administration and the short half-life period of antibodies in the lungs by intranasal or aerosolized immunization, mRNA encoding broadly neutralizing antibodies with lung-targeting capability can perfectly provide high-titer antibodies in lungs to prevent the SARS-CoV-2 infection. Here, we firstly identify a human monoclonal antibody, 8-9D, with broad neutralizing potency against SARS-CoV-2 variants. The neutralization mechanism of this antibody is explained by the structural characteristics of 8-9D Fabs in complex with the Omicron BA.5 spike. In addition, we evaluate the efficacy of 8-9D using a safe and robust mRNA delivery platform and compare the performance of 8-9D when its mRNA is and is not selectively delivered to the lungs. The lung-selective delivery of the 8-9D mRNA enables the expression of neutralizing antibodies in the lungs which blocks the invasion of the virus, thus effectively protecting female K18-hACE2 transgenic mice from challenge with the Beta or Omicron BA.1 variant. Our work underscores the potential application of lung-selective mRNA antibodies in the prevention and treatment of infections caused by circulating SARS-CoV-2 variants.

Suggested Citation

  • Wanbo Tai & Kai Yang & Yubin Liu & Ruofan Li & Shengyong Feng & Benjie Chai & Xinyu Zhuang & Shaolong Qi & Huicheng Shi & Zhida Liu & Jiaqi Lei & Enhao Ma & Weixiao Wang & Chongyu Tian & Ting Le & Jin, 2023. "A lung-selective delivery of mRNA encoding broadly neutralizing antibody against SARS-CoV-2 infection," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43798-8
    DOI: 10.1038/s41467-023-43798-8
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