Structural basis of broad protection against influenza virus by human antibodies targeting the neuraminidase active site via a recurring motif in CDR H3.

ABSTRACT: Influenza viruses evolve rapidly, driving seasonal epidemics and posing global pandemic threats. While neuraminidase (NA) has emerged as a vaccine target, shared molecular features of NA antibody responses are still not well understood. Here, we describe cryo-electron microscopy structures of the broadly protective human antibody DA03E17, which was previously identified from an H1N1-infected donor, in complex with NA from A/H1N1, A/H3N2, and B/Victoria-lineage viruses. DA03E17 targets the highly conserved NA active site using its long CDR H3, which features a DR (Asp-Arg) motif that engages catalytic residues and mimics sialic acid interactions. We further demonstrate that this motif is conserved among several NA active site-targeting antibodies, indicating a common receptor mimicry strate

SUBMITTER: Jo G 

PROVIDER: S-EPMC12316933 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature