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TitlePotently neutralizing and protective anti-human metapneumovirus antibodies target diverse sites on the fusion glycoprotein.
Journal, issue, pagesImmunity, Vol. 55, Issue 9, Page 1710-11724.e8, Year 2022
Publish dateSep 13, 2022
AuthorsC Garrett Rappazzo / Ching-Lin Hsieh / Scott A Rush / Emma S Esterman / Teresa Delgado / James C Geoghegan / Anna Z Wec / Mrunal Sakharkar / Vicente Más / Jason S McLellan / Laura M Walker /
PubMed AbstractHuman metapneumovirus (hMPV) is a leading cause of acute lower respiratory tract infections in high-risk populations, yet there are no vaccines or anti-viral therapies approved for the prevention or ...Human metapneumovirus (hMPV) is a leading cause of acute lower respiratory tract infections in high-risk populations, yet there are no vaccines or anti-viral therapies approved for the prevention or treatment of hMPV-associated disease. Here, we used a high-throughput single-cell technology to interrogate memory B cell responses to the hMPV fusion (F) glycoprotein in young adult and elderly donors. Across all donors, the neutralizing antibody response was primarily directed to epitopes expressed on both pre- and post-fusion F conformations. However, we identified rare, highly potent broadly neutralizing antibodies that recognize pre-fusion-specific epitopes and structurally characterized an antibody that targets a site of vulnerability at the pre-fusion F trimer apex. Additionally, monotherapy with neutralizing antibodies targeting three distinct antigenic sites provided robust protection against lower respiratory tract infection in a small animal model. This study provides promising monoclonal antibody candidates for passive immunoprophylaxis and informs the rational design of hMPV vaccine immunogens.
External linksImmunity / PubMed:35944529
MethodsEM (single particle)
Resolution3.46 Å
Structure data

27024

8cw9

EMDB-27024, PDB-8cw9:
Prefusion-stabilized hMPV fusion protein bound to ADI-61026 and MPE8 Fabs
Method: EM (single particle) / Resolution: 3.46 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

Source
  • human metapneumovirus
  • homo sapiens (human)
KeywordsVIRAL PROTEIN/Immune System / Site 0 neutralizing antibody / Prefusion-stabilized hMPV F protein / VIRAL PROTEIN / VIRAL PROTEIN-Immune System complex

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