8J1T

Local refined cryo-EM structure of Omicron BA.5 RBD in complex with 8-9D Fab

Summary for 8J1T

• Entry DOI: 10.2210/pdb8j1t/pdb
• EMDB information: 35932
• Descriptor: 8-9D heavy chain, 8-9D light chain, Spike protein (3 entities in total)
• Functional Keywords: viral protein-immune system complex, viral protein/immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 3
• Total formula weight: 46074.63

Authors

Xiang, Y.,Li, R. (deposition date: 2023-04-13, release date: 2023-11-29, Last modification date: 2024-10-23)

Primary citation

Tai, W.,Yang, K.,Liu, Y.,Li, R.,Feng, S.,Chai, B.,Zhuang, X.,Qi, S.,Shi, H.,Liu, Z.,Lei, J.,Ma, E.,Wang, W.,Tian, C.,Le, T.,Wang, J.,Chen, Y.,Tian, M.,Xiang, Y.,Yu, G.,Cheng, G.
A lung-selective delivery of mRNA encoding broadly neutralizing antibody against SARS-CoV-2 infection.
Nat Commun, 14:8042-8042, 2023

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 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.

PubMed: 38052844
DOI: 10.1038/s41467-023-43798-8

Experimental method

ELECTRON MICROSCOPY (3.3 Å)