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Updated: Dec 6, 2025
Peptide Scanning-assisted Identification of a Monoclonal Antibody-recognized Linear B-cell Epitope
Published on: March 24, 2017
Antibody recognition of the Pneumovirus fusion protein trimer interface
Jiachen Huang1,2, Darren Diaz1,2, Jarrod J Mousa1,2
1Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA, United States of America.
Abstract:
Human metapneumovirus (hMPV) is a leading cause of viral respiratory infection in children, and can cause severe lower respiratory tract infection in infants, the elderly, and immunocompromised patients. However, there remain no licensed vaccines or specific treatments for hMPV infection. Although the hMPV fusion (F) protein is the sole target of neutralizing antibodies, the immunological properties of hMPV F remain poorly understood. To further define the humoral immune response to the hMPV F protein, we isolated two new human monoclonal antibodies (mAbs), MPV458 and MPV465. Both mAbs are neutralizing in vitro and were determined to target a unique antigenic site using competitive biolayer interferometry. We determined both MPV458 and MPV465 have higher affinity for monomeric hMPV F than trimeric hMPV F. MPV458 was co-crystallized with hMPV F, and the mAb primarily interacts with an alpha helix on the F2 region of the hMPV F protein. Surprisingly, the major epitope for MPV458 lies within the trimeric interface of the hMPV F protein, suggesting significant breathing of the hMPV F protein must occur for host immune recognition of the novel epitope. In addition, significant glycan interactions were observed with a somatically mutated light chain framework residue. The data presented identifies a novel epitope on the hMPV F protein for epitope-based vaccine design, and illustrates a new mechanism for human antibody neutralization of viral glycoproteins.
Insights
Researchers identified a new target site on the human metapneumovirus (hMPV) fusion (F) protein, crucial for developing effective vaccines and treatments against this common respiratory virus.
Area of Science:
- Virology
- Immunology
- Structural Biology
Background:
- Human metapneumovirus (hMPV) causes significant respiratory illness, especially in vulnerable populations.
- No licensed vaccines or specific antiviral therapies currently exist for hMPV.
- The hMPV fusion (F) protein is a key target for neutralizing antibodies, but its immunological properties are not fully understood.
Purpose of the Study:
- To characterize the humoral immune response to the hMPV F protein.
- To identify novel antigenic sites on the hMPV F protein for therapeutic and vaccine development.
Main Methods:
- Isolation and characterization of human monoclonal antibodies (mAbs) MPV458 and MPV465.
- In vitro neutralization assays and competitive biolayer interferometry to assess antibody binding and epitope mapping.
- Co-crystallization of mAb MPV458 with the hMPV F protein to determine structural interactions.
Main Results:
- Two novel neutralizing human mAbs, MPV458 and MPV465, were identified.
- These mAbs bind to a unique antigenic site on the hMPV F protein, with higher affinity for the monomeric form.
- Structural analysis revealed mAb MPV458 targets an epitope within the F protein's trimeric interface, involving interactions with the F2 region and a glycan.
Conclusions:
- A novel epitope on the hMPV F protein has been identified, offering a new avenue for epitope-based vaccine design.
- The findings reveal a unique mechanism of antibody neutralization involving interactions with the F protein's trimeric interface and associated glycans.
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