A common solution to group 2 influenza virus neutralization

RHE Friesen, PS Lee, EJM Stoop… - Proceedings of the …, 2014 - National Acad Sciences
RHE Friesen, PS Lee, EJM Stoop, RMB Hoffman, DC Ekiert, G Bhabha, W Yu, J Juraszek
Proceedings of the National Academy of Sciences, 2014National Acad Sciences
The discovery and characterization of broadly neutralizing antibodies (bnAbs) against
influenza viruses have raised hopes for the development of monoclonal antibody (mAb)-
based immunotherapy and the design of universal influenza vaccines. Only one human
bnAb (CR8020) specifically recognizing group 2 influenza A viruses has been previously
characterized that binds to a highly conserved epitope at the base of the hemagglutinin (HA)
stem and has neutralizing activity against H3, H7, and H10 viruses. Here, we report a …
The discovery and characterization of broadly neutralizing antibodies (bnAbs) against influenza viruses have raised hopes for the development of monoclonal antibody (mAb)-based immunotherapy and the design of universal influenza vaccines. Only one human bnAb (CR8020) specifically recognizing group 2 influenza A viruses has been previously characterized that binds to a highly conserved epitope at the base of the hemagglutinin (HA) stem and has neutralizing activity against H3, H7, and H10 viruses. Here, we report a second group 2 bnAb, CR8043, which was derived from a different germ-line gene encoding a highly divergent amino acid sequence. CR8043 has in vitro neutralizing activity against H3 and H10 viruses and protects mice against challenge with a lethal dose of H3N2 and H7N7 viruses. The crystal structure and EM reconstructions of the CR8043-H3 HA complex revealed that CR8043 binds to a site similar to the CR8020 epitope but uses an alternative angle of approach and a distinct set of interactions. The identification of another antibody against the group 2 stem epitope suggests that this conserved site of vulnerability has great potential for design of therapeutics and vaccines.
National Acad Sciences