Antibody 3CF5 neutralizes historical and emerging H5Nx influenza viruses by targeting a conserved non-receptor-binding hemagglutinin epitope.

Antibody 3CF5 neutralizes multiple H5Nx influenza viruses across 1997–2024, including contemporary clade 2.3.4.4b H5N1 strains linked to an ongoing dairy cattle outbreak.

• Why it matters: H5Nx avian influenza viruses remain persistent pandemic threats, and broadly neutralizing antibodies that work against both historical and emerging strains are needed.
• What they did: Rhesus macaques were immunized with an H5N6 vaccine to generate 30 H5-reactive monoclonal antibodies, and 3CF5 was mapped by cryo-EM to a conserved non-receptor-binding HA head epitope.
• The result: 3CF5 inhibits membrane fusion and shows antibody-dependent cellular cytotoxicity, and converting 3CF5-IgG to mucosal secretory IgA1 enhances neutralization against H5N1 up to 128-fold.

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