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

文献类型： 外文期刊

第一作者： Tai, Wanbo

作者： Tai, Wanbo;Wang, Weixiao;Tian, Chongyu;Le, Ting;Wang, Jinyong;Chen, Yunfeng;Cheng, Gong;Tai, Wanbo;Wang, Weixiao;Tian, Chongyu;Le, Ting;Wang, Jinyong;Chen, Yunfeng;Yang, Kai;Yu, Guocan;Cheng, Gong;Li, Ruofan;Xiang, Ye;Zhuang, Xinyu;Tian, Mingyao;Liu, Zhida

作者机构：

期刊名称：NATURE COMMUNICATIONS （ 影响因子：16.6； 五年影响因子：17.0 ）

ISSN：

年卷期： 2023 年 14 卷 1 期

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收录情况： SCI

摘要： 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 complexwith 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 itsmRNA 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.

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