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Updated: Jan 7, 2026
A Method to Assess Fc-mediated Effector Functions Induced by Influenza Hemagglutinin Specific Antibodies
Published on: February 23, 2018
Structural basis for childhood antibody recognition of the human metapneumovirus fusion protein
Ahmed Magdy Khalil1,2, Behrouz Ghazi Esfahani1, Rose J Miller3,4
1Department of Biomedical Sciences, College of Medicine, Florida State University, Tallahassee, FL, USA.
Abstract:
Human metapneumovirus (hMPV) is a significant cause of acute respiratory illness in children and older adults, with most children becoming seropositive by five years of age. The hMPV fusion (F) protein is the sole target of neutralizing antibodies, and while most common B-cell-targeted neutralizing epitopes on the hMPV F protein have been determined in hMPV-infected adults, the antibody response in hMPV-infected children remains undefined. We isolate five human monoclonal antibodies (mAbs) from hMPV-infected children, and evaluate their binding avidity, neutralization potency, epitope specificity, and in vivo efficacy. All mAbs are neutralizing, and epitope binning reveals four different epitopes targeted by the mAbs. Cryo-EM structures of four mAbs in complex with the hMPV F protein reveal epitopes on the hMPV F trimer surface as well as an intratrimer epitope located completely within the hMPV F trimer interface. Furthermore, we determine the prophylactic efficacy of the mAbs in protection against hMPV challenge in mice. These findings provide new insights into the immunodominant antigenic epitopes on the hMPV F protein in children and identify new mAbs for hMPV F disease prevention.
Insights
Researchers identified five human monoclonal antibodies (mAbs) from children infected with human metapneumovirus (hMPV). These mAbs target distinct epitopes on the hMPV fusion (F) protein, offering potential for hMPV disease prevention.
Area of Science:
- Virology
- Immunology
- Structural Biology
Background:
- Human metapneumovirus (hMPV) causes significant respiratory illness in children and older adults.
- Neutralizing antibodies target the hMPV fusion (F) protein, but pediatric antibody responses and epitopes are not well understood.
- Understanding pediatric immune responses is crucial for developing effective hMPV therapeutics.
Purpose of the Study:
- To characterize the antibody response to hMPV infection in children.
- To identify novel neutralizing epitopes on the hMPV F protein targeted by pediatric antibodies.
- To evaluate the therapeutic potential of pediatric-derived monoclonal antibodies (mAbs) against hMPV.
Main Methods:
- Isolation and characterization of five human monoclonal antibodies (mAbs) from hMPV-infected children.
- Assessment of mAb binding avidity, neutralization potency, and epitope specificity.
- Determination of cryo-electron microscopy (cryo-EM) structures of mAbs complexed with the hMPV F protein.
- Evaluation of in vivo prophylactic efficacy of mAbs in a mouse model.
Main Results:
- All five isolated mAbs demonstrated neutralizing activity against hMPV.
- Epitope binning identified four distinct neutralizing epitopes targeted by the mAbs.
- Cryo-EM structures revealed epitopes on the F protein surface and within the F trimer interface.
- Prophylactic administration of mAbs provided protection against hMPV challenge in mice.
Conclusions:
- This study elucidates immunodominant antigenic epitopes on the hMPV F protein in children.
- Identified pediatric-derived mAbs represent promising candidates for hMPV disease prevention.
- Findings advance understanding of pediatric humoral immunity against hMPV.
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