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

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2024.11.26.625467v1

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 strategy. We also identified potential antibody precursors containing this DR motif in all donors of a healthy human donor BCR database, highlighting the prevalence of this motif and its potential as vaccine targeting. Our findings reveal shared molecular features in NA active site-targeting antibodies, offering insights for NA-based universal influenza vaccine design.

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#aH3n2 #abstract #biology #h1n1pdm09 #health #immunology #influenzaA #monoclonalAntibodies #research #vaccine