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Updated: Aug 28, 2025
A Method to Assess Fc-mediated Effector Functions Induced by Influenza Hemagglutinin Specific Antibodies
Published on: February 23, 2018
Characterization of prefusion-F-specific antibodies elicited by natural infection with human metapneumovirus
Scott A Rush1, Gurpreet Brar2, Ching-Lin Hsieh1
1Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.
Abstract:
Human metapneumovirus (hMPV) is a major cause of acute respiratory infections in infants and older adults, for which no vaccines or therapeutics are available. The viral fusion (F) glycoprotein is required for entry and is the primary target of neutralizing antibodies; however, little is known about the humoral immune response generated from natural infection. Here, using prefusion-stabilized F proteins to interrogate memory B cells from two older adults, we obtain over 700 paired non-IgM antibody sequences representing 563 clonotypes, indicative of a highly polyclonal response. Characterization of 136 monoclonal antibodies reveals broad recognition of the protein surface, with potently neutralizing antibodies targeting each antigenic site. Cryo-EM studies further reveal two non-canonical sites and the molecular basis for recognition of the apex of hMPV F by two prefusion-specific neutralizing antibodies. Collectively, these results provide insight into the humoral response to hMPV infection in older adults and will help guide vaccine development.
Insights
Human metapneumovirus (hMPV) infection elicits a diverse antibody response in older adults. Researchers identified potent neutralizing antibodies targeting the hMPV fusion (F) protein, crucial for vaccine development.
Area of Science:
- Virology
- Immunology
- Structural Biology
Background:
- Human metapneumovirus (hMPV) causes significant respiratory illness, particularly in vulnerable populations.
- Currently, no vaccines or treatments exist for hMPV infections.
- The viral fusion (F) glycoprotein is a key target for neutralizing antibodies, but the natural immune response is poorly understood.
Purpose of the Study:
- To investigate the humoral immune response to hMPV infection in older adults.
- To characterize the antibody repertoire targeting the hMPV F protein.
- To inform the development of hMPV vaccines and therapeutics.
Main Methods:
- Analysis of memory B cell antibody sequences from older adults post-hMPV infection.
- Production and characterization of monoclonal antibodies against the hMPV F protein.
- Cryo-electron microscopy (Cryo-EM) to determine structural details of antibody-F protein interactions.
Main Results:
- A highly polyclonal antibody response involving 563 distinct clonotypes was observed.
- 136 monoclonal antibodies demonstrated broad recognition of the F protein surface.
- Potently neutralizing antibodies were identified targeting multiple antigenic sites, including two novel non-canonical sites.
Conclusions:
- Natural hMPV infection in older adults generates a broad and potent neutralizing antibody response.
- Structural insights reveal key vulnerable sites on the hMPV F protein.
- These findings provide a foundation for designing effective hMPV vaccines.
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