EMD-35934
Cryo-EM reconstruction of SARS-CoV2 Omicron BA.5 spike in complex with 8-9D Fabs
EMD-35934
Single-particle3.01 Å
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Map released: 29/11/2023
Last modified: 09/10/2024
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
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
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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
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(2023) Nat Commun , 14 , 8042 - 8042
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.
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.