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Structural basis for a potent #human neutralizing #antibody targeting a conserved epitope on the #H7 #hemagglutinin head

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By G.M.

 


Significance

The high-resolution cryo-EM structure indicates that the human antibody 6Y13 binds strongly to a conserved pan-H7 epitope on the hemagglutinin head, distinct from the receptor-binding site and lateral patch. However, 6Y13 can broadly neutralize H7 viruses, fully protect H7N9-infected mice, and potently block receptor binding through mechanisms, independent of Fc-mediated steric hindrance.


Abstract

Zoonotic H7N9 avian influenza virus infection remains a global concern because of its pandemic potential. Therefore, developing effective antibodies and vaccines against H7N9 is vital for preventing and controlling major outbreaks. Here, we isolated a human VH3-30 gene-encoded antibody, designated 6Y13, from a survivor of H7N9 infection. This antibody recognized the hemagglutinins (HAs) of the representative H7 subtype zoonotic viruses spanning two decades of antigenic evolution and potently neutralized epidemic H7N9 viruses in vitro. Moreover, 6Y13 conferred complete protection in mice against lethal H7N9 challenge in both prophylactic and therapeutic experiments. Structural analysis by cryoelectron microscopy indicated that 6Y13 binds to a unique conserved site on the HA head, distinct from the receptor-binding site and lateral patch. Nevertheless, 6Y13 efficiently blocked viral receptor binding without interfering with HA receptor binding, independent of Fc-mediated steric hindrance. Our findings provide a promising therapeutic candidate against pan-H7 subtype viruses and are beneficial for the design of H7 subtype influenza vaccine immunogens.

Source: Proceedings of the National Academy of Sciences of the United States of America, https://www.pnas.org/doi/10.1073/pnas.2503008122

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