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| Title | Structural basis for ultrapotent antibody-mediated neutralization of human metapneumovirus. |
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| Journal, issue, pages | Proc Natl Acad Sci U S A, Vol. 119, Issue 25, Page e2203326119, Year 2022 |
| Publish date | Jun 21, 2022 |
 Authors | Avik Banerjee / Jiachen Huang / Scott A Rush / Jackelyn Murray / Aaron D Gingerich / Fredejah Royer / Ching-Lin Hsieh / Ralph A Tripp / Jason S McLellan / Jarrod J Mousa /  |
| PubMed Abstract | Human metapneumovirus (hMPV) is a leading cause of morbidity and hospitalization among children worldwide, however, no vaccines or therapeutics are currently available for hMPV disease prevention and ...Human metapneumovirus (hMPV) is a leading cause of morbidity and hospitalization among children worldwide, however, no vaccines or therapeutics are currently available for hMPV disease prevention and treatment. The hMPV fusion (F) protein is the sole target of neutralizing antibodies. To map the immunodominant epitopes on the hMPV F protein, we isolated a panel of human monoclonal antibodies (mAbs), and the mAbs were assessed for binding avidity, neutralization potency, and epitope specificity. We found the majority of the mAbs target diverse epitopes on the hMPV F protein, and we discovered multiple mAb binding approaches for antigenic site III. The most potent mAb, MPV467, which had picomolar potency, was examined in prophylactic and therapeutic mouse challenge studies, and MPV467 limited virus replication in mouse lungs when administered 24 h before or 72 h after viral infection. We determined the structure of MPV467 in complex with the hMPV F protein using cryo-electron microscopy to a resolution of 3.3 Å, which revealed a complex novel prefusion-specific epitope overlapping antigenic sites II and V on a single protomer. Overall, our data reveal insights into the immunodominant antigenic epitopes on the hMPV F protein, identify a mAb therapy for hMPV F disease prevention and treatment, and provide the discovery of a prefusion-specific epitope on the hMPV F protein. |
 External links | Proc Natl Acad Sci U S A / PubMed:35696580 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 3.34 Å |
| Structure data | EMDB-26704, PDB-7ur4: |
| Chemicals |  ChemComp-NAG: |
| Source |
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 Keywords |  VIRAL PROTEIN/IMMUNE SYSTEM / neutralizing antibody / fusion protein / metapneumovirus / VIRAL PROTEIN-IMMUNE SYSTEM complex |
