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Updated: Sep 8, 2025
A Method to Assess Fc-mediated Effector Functions Induced by Influenza Hemagglutinin Specific Antibodies
Published on: February 23, 2018
Structural basis for ultrapotent antibody-mediated neutralization of human metapneumovirus
Avik Banerjee1, Jiachen Huang1,2, Scott A Rush3
1Center for Vaccines and Immunology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602.
Abstract:
Human metapneumovirus (hMPV) is a leading cause of morbidity and hospitalization among children worldwide, however, no vaccines or therapeutics are currently available for hMPV disease prevention and treatment. The hMPV fusion (F) protein is the sole target of neutralizing antibodies. To map the immunodominant epitopes on the hMPV F protein, we isolated a panel of human monoclonal antibodies (mAbs), and the mAbs were assessed for binding avidity, neutralization potency, and epitope specificity. We found the majority of the mAbs target diverse epitopes on the hMPV F protein, and we discovered multiple mAb binding approaches for antigenic site III. The most potent mAb, MPV467, which had picomolar potency, was examined in prophylactic and therapeutic mouse challenge studies, and MPV467 limited virus replication in mouse lungs when administered 24 h before or 72 h after viral infection. We determined the structure of MPV467 in complex with the hMPV F protein using cryo-electron microscopy to a resolution of 3.3 Å, which revealed a complex novel prefusion-specific epitope overlapping antigenic sites II and V on a single protomer. Overall, our data reveal insights into the immunodominant antigenic epitopes on the hMPV F protein, identify a mAb therapy for hMPV F disease prevention and treatment, and provide the discovery of a prefusion-specific epitope on the hMPV F protein.
Insights
Human metapneumovirus (hMPV) causes significant childhood illness. Researchers identified a potent monoclonal antibody (mAb), MPV467, targeting the hMPV fusion (F) protein, offering a potential therapy for hMPV infections.
Area of Science:
- Virology
- Immunology
- Structural Biology
Background:
- Human metapneumovirus (hMPV) is a major cause of respiratory illness and hospitalization in children globally.
- Currently, no vaccines or therapeutics exist for hMPV infection prevention or treatment.
Purpose of the Study:
- To map immunodominant epitopes on the hMPV fusion (F) protein.
- To identify and characterize potent neutralizing monoclonal antibodies (mAbs) against hMPV.
- To discover novel therapeutic strategies for hMPV disease.
Main Methods:
- Isolation and characterization of human monoclonal antibodies (mAbs) targeting the hMPV F protein.
- Assessment of mAb binding avidity, neutralization potency, and epitope specificity.
- Cryo-electron microscopy was used to determine the structure of a potent mAb in complex with the hMPV F protein.
Main Results:
- The majority of isolated mAbs targeted diverse epitopes on the hMPV F protein.
- A highly potent mAb, MPV467, demonstrated picomolar neutralization activity.
- MPV467 limited hMPV replication in mouse models when administered prophylactically or therapeutically.
- Structural analysis revealed MPV467 binds a novel, prefusion-specific epitope overlapping antigenic sites II and V.
Conclusions:
- The study provides insights into immunodominant antigenic epitopes on the hMPV F protein.
- MPV467 represents a promising mAb therapy candidate for hMPV disease prevention and treatment.
- A novel prefusion-specific epitope on the hMPV F protein was discovered.
