tetano
Editor, Senior Moderator
Nat Commun
. 2025 Aug 1;16(1):7067.
doi: 10.1038/s41467-025-62174-2. Structural basis of broad protection against influenza virus by human antibodies targeting the neuraminidase active site via a recurring motif in CDR H3
Gyunghee Jo[SUP] 1 [/SUP], Seiya Yamayoshi[SUP] 2 3 4 5 [/SUP], Krystal M Ma[SUP] 6 7 8 [/SUP], Olivia Swanson[SUP] 1 [/SUP], Jonathan L Torres[SUP] 1 [/SUP], James A Ferguson[SUP] 1 [/SUP], Monica L Fernández-Quintero[SUP] 1 [/SUP], Jiachen Huang[SUP] 1 [/SUP], Jeffrey Copps[SUP] 1 [/SUP], Alesandra J Rodriguez[SUP] 1 [/SUP], Jon M Steichen[SUP] 6 7 8 [/SUP], Yoshihiro Kawaoka[SUP] 2 4 5 9 [/SUP], Julianna Han[SUP] 10 [/SUP], Andrew B Ward[SUP] 11 [/SUP]
Affiliations
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 BCR sequences containing this DR motif across all donors in a healthy human repertoire database, suggesting that such precursors may be relatively common and have vaccine targeting potential. Our findings reveal shared molecular features in NA active site-targeting antibodies that can be harnessed to design broad, immune-focused influenza vaccines.
. 2025 Aug 1;16(1):7067.
doi: 10.1038/s41467-025-62174-2. Structural basis of broad protection against influenza virus by human antibodies targeting the neuraminidase active site via a recurring motif in CDR H3
Gyunghee Jo[SUP] 1 [/SUP], Seiya Yamayoshi[SUP] 2 3 4 5 [/SUP], Krystal M Ma[SUP] 6 7 8 [/SUP], Olivia Swanson[SUP] 1 [/SUP], Jonathan L Torres[SUP] 1 [/SUP], James A Ferguson[SUP] 1 [/SUP], Monica L Fernández-Quintero[SUP] 1 [/SUP], Jiachen Huang[SUP] 1 [/SUP], Jeffrey Copps[SUP] 1 [/SUP], Alesandra J Rodriguez[SUP] 1 [/SUP], Jon M Steichen[SUP] 6 7 8 [/SUP], Yoshihiro Kawaoka[SUP] 2 4 5 9 [/SUP], Julianna Han[SUP] 10 [/SUP], Andrew B Ward[SUP] 11 [/SUP]
Affiliations
- PMID: 40750588
- PMCID: PMC12316933
- DOI: 10.1038/s41467-025-62174-2
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 BCR sequences containing this DR motif across all donors in a healthy human repertoire database, suggesting that such precursors may be relatively common and have vaccine targeting potential. Our findings reveal shared molecular features in NA active site-targeting antibodies that can be harnessed to design broad, immune-focused influenza vaccines.