EMD-35934

Single-particle
3.01 Å
EMD-35934 Deposition: 13/04/2023
Map released: 29/11/2023
Last modified: 09/10/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-35934

Cryo-EM reconstruction of SARS-CoV2 Omicron BA.5 spike in complex with 8-9D Fabs

EMD-35934

Single-particle
3.01 Å
EMD-35934 Deposition: 13/04/2023
Map released: 29/11/2023
Last modified: 09/10/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Homo sapiens, Severe acute respiratory syndrome coronavirus 2
Sample: Severe acute respiratory syndrome coronavirus 2 Omicron BA.5 spike bound 8-9D Fab
Fitted models: 8j1v (Avg. Q-score: 0.374)

Deposition Authors: Xiang Y , Li R, Li R
A lung-selective delivery of mRNA encoding broadly neutralizing antibody against SARS-CoV-2 infection.
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
(2023) Nat Commun , 14 , 8042 - 8042
PUBMED: 38052844
DOI: doi:10.1038/s41467-023-43798-8
ISSN: 2041-1723
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.