Related Experiment Video
Updated: Sep 19, 2025
Detection of Neutralization-sensitive Epitopes in Antigens Displayed on Virus-Like Particle VLP-Based Vaccines Using a Capture Assay
Published on: February 10, 2022
Potent neutralization of Marburg virus by a vaccine-elicited monoclonal antibody
Amin Addetia1, Lisa Perruzza2, Young-Jun Park1,3
1Department of Biochemistry, University of Washington, Seattle, WA, 9815, USA.
Abstract:
Marburg virus (MARV) is a filovirus that causes a severe and often lethal hemorrhagic fever. Despite the increasing frequency of MARV outbreaks, no vaccines or therapeutics are licensed for use in humans. Here, we designed mutations that improve the expression and thermostability of the prefusion MARV glycoprotein (GP) ectodomain trimer, which is the sole target of neutralizing antibodies and vaccines in development. We discovered a fully human monoclonal antibody, MARV16, that broadly neutralizes all MARV isolates as well as Ravn virus and Dehong virus with 40 to 100-fold increased potency relative to previously described antibodies. We determined a cryo-electron microscopy structure of MARV16-bound MARV GP showing that MARV16 recognizes a prefusion-specific epitope spanning GP1 and GP2, blocking receptor binding and preventing conformational changes required for viral entry. We further reveal the architecture of the MARV GP glycan cap, which shields the receptor binding site (RBS), underscoring architectural similarities with distantly related filovirus GPs. MARV16 and previously identified RBS-directed antibodies can bind MARV GP simultaneously, paving the way for a MARV therapeutic antibody cocktail. MARV GP stabilization along with the discovery of a potent neutralizing antibody will advance treatment and prevention options for MARV.
Insights
Researchers developed a stabilized Marburg virus glycoprotein (GP) and discovered MARV16, a potent antibody that neutralizes Marburg virus (MARV) and related viruses, advancing potential treatments.
Area of Science:
- Virology
- Immunology
- Structural Biology
Background:
- Marburg virus (MARV) causes severe hemorrhagic fever with no licensed treatments.
- The MARV glycoprotein (GP) is a key target for vaccines and antibody therapies.
- MARV outbreaks are increasing in frequency.
Purpose of the Study:
- To improve the expression and thermostability of the MARV prefusion glycoprotein (GP) trimer.
- To discover novel neutralizing monoclonal antibodies against MARV.
- To characterize the interaction between MARV GP and neutralizing antibodies.
Main Methods:
- Protein engineering to enhance MARV GP expression and stability.
- Monoclonal antibody discovery and characterization.
- Cryo-electron microscopy (cryo-EM) for structural analysis.
- Viral neutralization assays.
Main Results:
- Designed mutations improved MARV prefusion GP ectodomain trimer expression and thermostability.
- Discovered MARV16, a human monoclonal antibody with broad and potent neutralization of MARV, Ravn virus, and Dehong virus.
- Determined the cryo-EM structure of MARV16 bound to MARV GP, revealing a prefusion-specific epitope that blocks viral entry.
- Elucidated the MARV GP glycan cap structure, showing similarities to other filovirus GPs.
- Demonstrated that MARV16 and other receptor binding site (RBS)-directed antibodies can bind simultaneously.
Conclusions:
- Stabilized MARV GP and the potent MARV16 antibody represent significant advancements for MARV therapeutic and vaccine development.
- MARV16's broad neutralization and unique epitope offer a promising candidate for Marburg virus treatment.
- The potential for an antibody cocktail combining MARV16 with other RBS-directed antibodies could enhance therapeutic efficacy.
