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Antibody 27F3 Broadly Targets Influenza A Group 1 and 2 Hemagglutinins through a Further Variation in VH1-69 Antibody Orientation on the HA Stem

tetano

Editor, Senior Moderator
Cell Rep. 2017 Sep 19;20(12):2935-2943. doi: 10.1016/j.celrep.2017.08.084.
[h=1]Antibody 27F3 Broadly Targets Influenza A Group 1 and 2 Hemagglutinins through a Further Variation in VH1-69 Antibody Orientation on the HA Stem.[/h] Lang S[SUP]1[/SUP], Xie J[SUP]2[/SUP], Zhu X[SUP]3[/SUP], Wu NC[SUP]3[/SUP], Lerner RA[SUP]4[/SUP], Wilson IA[SUP]5[/SUP].
[h=3]Author information[/h]

[h=3]Abstract[/h] 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 V[SUB]H[/SUB]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 V[SUB]H[/SUB]1-69 antibodies to the HA stem. Compared to other V[SUB]H[/SUB]1-69 antibodies, the 27F3 V[SUB]H[/SUB] domain interacts with the HA stem in a distinct orientation, which alters its epitope and may have influenced its breadth. The diverse rotations of V[SUB]H[/SUB]1-69 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.
Copyright ? 2017 The Author(s). Published by Elsevier Inc. All rights reserved.


[h=4]KEYWORDS:[/h] V(H)1-69; antibody family; broadly neutralizing antibodies; crystal structure; hemagglutinin; influenza virus; phage display

PMID: 28930686 DOI: 10.1016/j.celrep.2017.08.084
 
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