[PDF][PDF] Antibody 27F3 broadly targets influenza A group 1 and 2 hemagglutinins through a further variation in VH1-69 antibody orientation on the HA stem

S Lang, J Xie, X Zhu, NC Wu, RA Lerner, IA Wilson - Cell reports, 2017 - cell.com
S Lang, J Xie, X Zhu, NC Wu, RA Lerner, IA Wilson
Cell reports, 2017cell.com
Antibodies that target both group 1 and group 2 influenza A viruses are valuable for
therapeutic and vaccine development, but only a few have been reported to date. Here, we
describe a new VH 1-69 antibody 27F3 that broadly recognizes heterosubtypic
hemagglutinins (HAs) from both group 1 and group 2 influenza A viruses. Structural
characterization of 27F3 Fab with A/California/04/2009 (H1N1) hemagglutinin illustrates that
27F3 shares the key binding features observed in other VH 1-69 antibodies to the HA stem …
Summary
Antibodies that target both group 1 and group 2 influenza A viruses are valuable for therapeutic and vaccine development, but only a few have been reported to date. Here, we describe a new VH1-69 antibody 27F3 that broadly recognizes heterosubtypic hemagglutinins (HAs) from both group 1 and group 2 influenza A viruses. Structural characterization of 27F3 Fab with A/California/04/2009 (H1N1) hemagglutinin illustrates that 27F3 shares the key binding features observed in other VH1-69 antibodies to the HA stem. Compared to other VH1-69 antibodies, the 27F3 VH domain interacts with the HA stem in a distinct orientation, which alters its epitope and may have influenced its breadth. The diverse rotations of VH1-69 antibodies on the HA stem epitope highlight the different ways that this antibody family can evolve to broadly neutralize influenza A viruses. These results have important implications for understanding how to elicit broad antibody responses against influenza virus.
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