Related Experiment Video
Updated: Jun 7, 2025
An Improved and High Throughput Respiratory Syncytial Virus RSV Micro-neutralization Assay
Published on: January 26, 2019
A pan-orthoebolavirus neutralizing antibody encoded by mRNA effectively prevents virus infection
Pengfei Fan1, Bingjie Sun1, Zixuan Liu1
1Laboratory of Advanced Biotechnology, Beijing Institute of Biotechnology, Beijing, People's Republic of China.
Abstract:
Orthoebolavirus is a genus of hazardous pathogens that has caused over 30 outbreaks. However, currently approved therapies are limited in scope, as they are only effective against the Ebola virus and lack cross-protection against other orthoebolaviruses. Here, we demonstrate that a previously isolated human-derived antibody, 2G1, can recognize the glycoprotein (GP) of every orthoebolavirus species. The cryo-electron microscopy structure of 2G1 Fab in complex with the GPΔMucin trimer reveals that 2G1 binds a quaternary pocket formed by three subunits from two GP protomers. 2G1 recognizes highly conserved epitopes among filoviruses and achieves neutralization by blocking GP proteolysis. We designed an efficient mRNA module capable of producing test antibodies at expression levels exceeding 1500 ng/mL in vitro. The lipid nanoparticle (LNP)-encapsulated mRNA-2G1 exhibited potent neutralizing activities against the HIV-pseudotyped Ebola and Sudan viruses that were 19.8 and 12.5 times that of IgG format, respectively. In mice, the antibodies encoded by the mRNA-2G1-LNP peaked within 24 h, effectively blocking the invasion of pseudoviruses with no apparent liver toxicity. This study suggests that the 2G1 antibody and its mRNA formulation represent promising candidate interventions for orthoebolavirus disease, and it provides an efficient mRNA framework applicable to antibody-based therapies.
Insights
A novel human antibody, 2G1, targets all orthoebolaviruses by binding conserved glycoprotein epitopes. mRNA-based delivery of this antibody shows potent cross-neutralization against Ebola and Sudan viruses in preclinical models.
Area of Science:
- Virology and Immunology
- Structural Biology
- Vaccine Technology
Background:
- Orthoebolavirus genus comprises hazardous pathogens responsible for numerous outbreaks.
- Current therapies for orthoebolavirus infections lack cross-protection against diverse species.
- Need for broad-spectrum interventions against emerging filovirus threats.
Purpose of the Study:
- To identify and characterize a broadly neutralizing antibody against orthoebolaviruses.
- To elucidate the structural basis of antibody-glycoprotein interaction.
- To develop and evaluate an mRNA-based delivery system for antibody therapy.
Main Methods:
- Isolation and characterization of human-derived antibody 2G1.
- Cryo-electron microscopy to determine the structure of antibody-GP complex.
- Design and synthesis of mRNA encoding antibody 2G1, encapsulated in lipid nanoparticles (LNPs).
- In vitro neutralization assays and in vivo studies in mouse models.
Main Results:
- Antibody 2G1 recognizes the glycoprotein (GP) of all orthoebolavirus species.
- Structural analysis revealed 2G1 binds a conserved quaternary pocket on the GP trimer.
- mRNA-2G1-LNP formulation demonstrated potent in vitro neutralization against Ebola and Sudan viruses.
- In vivo administration of mRNA-2G1-LNP in mice showed rapid antibody expression, effective pseudovirus neutralization, and no observed liver toxicity.
Conclusions:
- The 2G1 antibody offers broad neutralization against orthoebolaviruses by targeting conserved epitopes.
- mRNA-2G1-LNP represents a promising, rapidly deployable therapeutic strategy for orthoebolavirus diseases.
- The developed mRNA framework is applicable for future antibody-based therapies against viral pathogens.
Related Concept Videos
01:29Viruses with RNA Genomes
02:28Leaky Scanning
01:23RNA Interference
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...