{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"submitter":["Khalil AM"],"funding":["NIH, NIAID","NIAID NIH HHS"],"pubmed_abstract":["Human metapneumovirus (hMPV) is a significant cause of acute respiratory illness in children and adults, with the majority of children being seropositive for hMPV by five years of age. Infants, older adults, and immunocompromised individuals are more susceptible to severe hMPV infections that can lead to hospitalization and death. The hMPV fusion (F) protein is the sole target of neutralizing antibodies, and while the most common neutralizing epitopes on the hMPV F protein targeted by B cells in hMPV-infected adults have been previously determined, the antibody response in hMPV-infected children remains undefined. We isolated a panel of human monoclonal antibodies (mAbs) from children previously infected with hMPV (MPV498, MPV499, MPV510, MPV511, and MPV513), and the mAbs were assessed for binding avidity, neutralization potency, epitope specificity, and <i>in vivo</i> efficacy. All mAbs were neutralizing, and epitope binning revealed the presence of four different epitopes targeted by the mAbs. We determined the cryo-EM structures of four mAbs in complex with the hMPV F protein, which revealed epitopes located on the hMPV F trimer surface as well as an intratrimer epitope located completely within the hMPV F trimer interface. Furthermore, we determined the prophylactic efficacy of the mAbs in protection against hMPV challenge in mice. Overall, our data reveal new insights into the immunodominant antigenic epitopes on the hMPV F protein in children and identify new mAb therapies for hMPV F disease prevention."],"journal":["bioRxiv : the preprint server for biology"],"pagination":["2025.08.29.673069"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12424945"],"repository":["biostudies-literature"],"pubmed_title":["Structural Basis for Childhood Antibody Recognition of The Human Metapneumovirus Fusion Protein."],"pmcid":["PMC12424945"],"funding_grant_id":["U01 AI088654","R01 AI143865","HHS272201400006C","R01AI143865","U01AI088654"],"pubmed_authors":["Balmaseda A","Huang J","Khalil AM","Kuan G","Mousa JJ","Esfahani BG","Gordon A","Miller RJ"],"additional_accession":[]},"is_claimable":false,"name":"Structural Basis for Childhood Antibody Recognition of The Human Metapneumovirus Fusion Protein.","description":"Human metapneumovirus (hMPV) is a significant cause of acute respiratory illness in children and adults, with the majority of children being seropositive for hMPV by five years of age. Infants, older adults, and immunocompromised individuals are more susceptible to severe hMPV infections that can lead to hospitalization and death. The hMPV fusion (F) protein is the sole target of neutralizing antibodies, and while the most common neutralizing epitopes on the hMPV F protein targeted by B cells in hMPV-infected adults have been previously determined, the antibody response in hMPV-infected children remains undefined. We isolated a panel of human monoclonal antibodies (mAbs) from children previously infected with hMPV (MPV498, MPV499, MPV510, MPV511, and MPV513), and the mAbs were assessed for binding avidity, neutralization potency, epitope specificity, and <i>in vivo</i> efficacy. All mAbs were neutralizing, and epitope binning revealed the presence of four different epitopes targeted by the mAbs. We determined the cryo-EM structures of four mAbs in complex with the hMPV F protein, which revealed epitopes located on the hMPV F trimer surface as well as an intratrimer epitope located completely within the hMPV F trimer interface. Furthermore, we determined the prophylactic efficacy of the mAbs in protection against hMPV challenge in mice. Overall, our data reveal new insights into the immunodominant antigenic epitopes on the hMPV F protein in children and identify new mAb therapies for hMPV F disease prevention.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Sep","modification":"2026-07-02T03:13:43.383Z","creation":"2026-07-02T03:11:50.54Z"},"accession":"S-EPMC12424945","cross_references":{"pubmed":["40950197"],"doi":["10.1101/2025.08.29.673069"]}}