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Updated: Apr 8, 2026
A Method to Assess Fc-mediated Effector Functions Induced by Influenza Hemagglutinin Specific Antibodies
Published on: February 23, 2018
Structural and mechanistic basis for antibody neutralization of the measles fusion protein
Dawid S Zyla1, Roberta Della Marca2,3,4, Davide Lacarbonara2,3
1Center for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, CA, USA.
Abstract:
Measles virus (MeV) is a highly contagious pathogen and a major global health threat. Resurgent infections, driven by insufficient vaccine coverage, waning herd immunity, and the vulnerability of immunocompromised populations, highlight the urgent need for effective countermeasures. While most vaccine-elicited antibodies target the hemagglutinin (H) protein, antibodies against the fusion (F) protein are also potent inhibitors. However, the specific target sites on this class I fusion protein, which undergoes dramatic conformational changes during entry, remain insufficiently characterized. Here, we characterize four mAbs targeting distinct F conformations. Structural analyses map antibody interactions, revealing that three neutralizing mAbs recognize the metastable prefusion conformation, while a non-neutralizing mAb binds only the post-triggered state. Biophysical and functional assays define distinct mechanisms of action: neutralization occurs either by stabilizing the prefusion protein or by preventing the extended intermediate from completing fusion. Uniquely, we detect a novel mechanism where an antibody prematurely triggers F activation but blocks the subsequent refolding required for viral entry. These findings provide the first detailed mapping of neutralizing epitopes on MeV F, establishing a framework for the rational design of F-targeted interventions.
Insights
Researchers mapped key antibody targets on the measles virus fusion (F) protein. Understanding these sites provides a foundation for developing new measles virus therapies and vaccines.
Area of Science:
- Virology
- Immunology
- Structural Biology
Background:
- Measles virus (MeV) poses a significant global health risk due to resurgent infections.
- Antibodies targeting the MeV hemagglutinin (H) protein are common, but those against the fusion (F) protein are also crucial for inhibition.
- The precise epitopes on the MeV F protein, essential for viral entry, are not fully understood.
Purpose of the Study:
- To characterize neutralizing monoclonal antibodies (mAbs) targeting distinct conformations of the MeV F protein.
- To elucidate the structural basis and mechanisms of MeV F protein neutralization by antibodies.
- To establish a framework for designing novel F protein-targeted antiviral strategies.
Main Methods:
- Characterization of four distinct monoclonal antibodies (mAbs) against the measles virus fusion (F) protein.
- Utilizing structural analyses (e.g., X-ray crystallography, cryo-EM) to map antibody-epitope interactions.
- Employing biophysical and functional assays to determine antibody mechanisms of action and neutralization potency.
Main Results:
- Three of the four characterized neutralizing mAbs bind to the metastable prefusion conformation of the F protein.
- One non-neutralizing mAb was observed to bind only the post-triggered state of the F protein.
- Identified distinct neutralization mechanisms, including stabilization of the prefusion state, prevention of fusion intermediate progression, and a novel mechanism of premature F triggering.
- Provided the first detailed mapping of neutralizing epitopes on the MeV F protein.
Conclusions:
- The study provides a comprehensive structural and functional characterization of neutralizing epitopes on the measles virus F protein.
- Findings reveal diverse mechanisms by which antibodies neutralize MeV via the F protein.
- This work lays the groundwork for the rational design of F protein-based vaccines and therapeutics against measles virus.
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