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Title | A lung-selective delivery of mRNA encoding broadly neutralizing antibody against SARS-CoV-2 infection. |
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Journal, issue, pages | Nat Commun, Vol. 14, Issue 1, Page 8042, Year 2023 |
Publish date | Dec 5, 2023 |
Authors | 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 / Jinyong Wang / Yunfeng Chen / Mingyao Tian / Ye Xiang / Guocan Yu / Gong Cheng / |
PubMed 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 ...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. |
External links | Nat Commun / PubMed:38052844 / PubMed Central |
Methods | EM (single particle) |
Resolution | 3.01 - 3.3 Å |
Structure data | EMDB-35932: Local refined cryo-EM reconstruction of Omicron BA.5 RBD in complex with 8-9D Fab EMDB-35934: Cryo-EM reconstruction of SARS-CoV2 Omicron BA.5 spike in complex with 8-9D Fabs |
Chemicals | ChemComp-NAG: |
Source |
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Keywords | VIRAL PROTEIN/IMMUNE SYSTEM / VIRAL PROTEIN-IMMUNE SYSTEM complex |