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Updated: Jul 20, 2025
An Improved and High Throughput Respiratory Syncytial Virus RSV Micro-neutralization Assay
Published on: January 26, 2019
Potent cross-neutralization of respiratory syncytial virus and human metapneumovirus through a structurally conserved
Xiaolin Wen1, Naveenchandra Suryadevara2, Nurgun Kose2
1Department of Structural Biology, Stanford University School of Medical School, Stanford, CA 94305, USA.
Abstract:
Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) infections pose a significant health burden. Using pre-fusion conformation fusion (F) proteins, we isolated a panel of anti-F antibodies from a human donor. One antibody (RSV-199) potently cross-neutralized 8 RSV and hMPV strains by recognizing antigenic site III, which is partially conserved in RSV and hMPV F. Next, we determined the cryoelectron microscopy (cryo-EM) structures of RSV-199 bound to RSV F trimers, hMPV F monomers, and an unexpected dimeric form of hMPV F. These structures revealed how RSV-199 engages both RSV and hMPV F proteins through conserved interactions of the antibody heavy-chain variable region and how variability within heavy-chain complementarity-determining region 3 (HCDR3) can be accommodated at the F protein interface in site-III-directed antibodies. Furthermore, RSV-199 offered enhanced protection against RSV A and B strains and hMPV in cotton rats. These findings highlight the mechanisms of broad neutralization and therapeutic potential of RSV-199.
Insights
A novel antibody, RSV-199, effectively neutralizes both Respiratory Syncytial Virus (RSV) and human metapneumovirus (hMPV) by targeting a conserved site on their fusion proteins. This antibody demonstrated therapeutic potential in animal models, offering protection against both viruses.
Area of Science:
- Virology
- Immunology
- Structural Biology
Background:
- Respiratory Syncytial Virus (RSV) and human metapneumovirus (hMPV) cause significant respiratory illness.
- Developing broad-spectrum antivirals is crucial for public health.
Purpose of the Study:
- To identify and characterize a cross-neutralizing antibody against RSV and hMPV.
- To elucidate the structural basis for broad neutralization.
Main Methods:
- Isolation of anti-fusion (F) protein antibodies from a human donor.
- Cryoelectron microscopy (cryo-EM) to determine antibody-F protein complex structures.
- In vivo efficacy studies in cotton rat models.
Main Results:
- One antibody, RSV-199, potently cross-neutralized 8 strains of RSV and hMPV by targeting antigenic site III.
- Cryo-EM structures revealed conserved binding interactions and antibody HCDR3 variability accommodation.
- RSV-199 provided enhanced protection against RSV and hMPV infection in cotton rats.
Conclusions:
- RSV-199 exhibits broad neutralization of RSV and hMPV through conserved interactions at antigenic site III.
- Structural insights explain the antibody's mechanism for cross-reactivity.
- RSV-199 represents a promising therapeutic candidate for both RSV and hMPV infections.
