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TitleConserved sites on the influenza H1 and H3 hemagglutinin recognized by human antibodies.
Journal, issue, pagesSci Adv, Vol. 11, Issue 17, Page eadu9140, Year 2025
Publish dateApr 25, 2025
AuthorsDaniel P Maurer / Mya Vu / Ana Sofia Ferreira Ramos / Haley L Dugan / Paul Khalife / James C Geoghegan / Laura M Walker / Goran Bajic / Aaron G Schmidt /
PubMed AbstractMonoclonal antibodies (mAbs) targeting the influenza hemagglutinin (HA) can be used as prophylactics or templates for next-generation vaccines. Here, we isolated broad, subtype-neutralizing mAbs from ...Monoclonal antibodies (mAbs) targeting the influenza hemagglutinin (HA) can be used as prophylactics or templates for next-generation vaccines. Here, we isolated broad, subtype-neutralizing mAbs from human B cells recognizing the H1 or H3 HA "head" and a mAb engaging the conserved stem. The H1 mAbs bind the lateral patch epitope on HAs from 1933 to 2021 and a prepandemic swine H1N1 virus. We improved neutralization potency using directed evolution toward a contemporary H1 HA. Deep mutational scanning of four antigenically distinct H1N1 viruses identified potential viral escape pathways. For the H3 mAbs, we used cryo-electron microscopy to define their epitopes: One mAb binds the side of the HA head, accommodating the N133 glycan and a pocket underneath the receptor binding site; the other mAb recognizes an HA stem epitope that partially overlaps with previously characterized mAbs but with distinct antibody variable genes. Collectively, these mAbs identify conserved sites recognized by broadly-reactive mAbs that may be elicited by next-generation vaccines.
External linksSci Adv / PubMed:40267182 / PubMed Central
MethodsEM (single particle)
Resolution3.01 Å
Structure data

44451

9bdf

EMDB-44451, PDB-9bdf:
Influenza A virus Hemagglutinin H3/Darwin/6/2021 in complex with Fab ADI-85666
Method: EM (single particle) / Resolution: 3.01 Å

44452

9bdg

EMDB-44452, PDB-9bdg:
Influenza A virus Hemagglutinin H3/Darwin/6/2021 in complex with Fab ADI-85647
Method: EM (single particle) / Resolution: 3.01 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

Source
  • homo sapiens (human)
  • influenza a virus
KeywordsVIRAL PROTEIN / Hemagglutinin / Influenza A / Antibody / Fab

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