tetano
Editor, Senior Moderator
J Exp Med. 2019 Jan 25. pii: jem.20181624. doi: 10.1084/jem.20181624. [Epub ahead of print]
[h=1]Neuraminidase inhibition contributes to influenza A virus neutralization by anti-hemagglutinin stem antibodies.[/h] Kosik I[SUP]1[/SUP], Angeletti D[SUP]1[/SUP], Gibbs JS[SUP]1[/SUP], Angel M[SUP]1[/SUP], Takeda K[SUP]2[/SUP], Kosikova M[SUP]3[/SUP], Nair V[SUP]4[/SUP], Hickman HD[SUP]5[/SUP], Xie H[SUP]3[/SUP], Brooke CB[SUP]6[/SUP], Yewdell JW[SUP]7[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Broadly neutralizing antibodies (Abs) that bind the influenza virus hemagglutinin (HA) stem may enable universal influenza vaccination. Here, we show that anti-stem Abs sterically inhibit viral neuraminidase (NA) activity against large substrates, with activity inversely proportional to the length of the fibrous NA stalk that supports the enzymatic domain. By modulating NA stalk length in recombinant IAVs, we show that anti-stem Abs inhibit virus release from infected cells by blocking NA, accounting for their in vitro neutralization activity. NA inhibition contributes to anti-stem Ab protection in influenza-infected mice, likely due at least in part to NA-mediated inhibition of FcγR-dependent activation of innate immune cells by Ab bound to virions. Food and Drug Administration-approved NA inhibitors enhance anti-stem-based Fc-dependent immune cell activation, raising the possibility of therapeutic synergy between NA inhibitors and anti-stem mAb treatment in humans.
This is a work of the U.S. Government and is not subject to copyright protection in the United States. Foreign copyrights may apply.
PMID: 30683737 DOI: 10.1084/jem.20181624
[h=1]Neuraminidase inhibition contributes to influenza A virus neutralization by anti-hemagglutinin stem antibodies.[/h] Kosik I[SUP]1[/SUP], Angeletti D[SUP]1[/SUP], Gibbs JS[SUP]1[/SUP], Angel M[SUP]1[/SUP], Takeda K[SUP]2[/SUP], Kosikova M[SUP]3[/SUP], Nair V[SUP]4[/SUP], Hickman HD[SUP]5[/SUP], Xie H[SUP]3[/SUP], Brooke CB[SUP]6[/SUP], Yewdell JW[SUP]7[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Broadly neutralizing antibodies (Abs) that bind the influenza virus hemagglutinin (HA) stem may enable universal influenza vaccination. Here, we show that anti-stem Abs sterically inhibit viral neuraminidase (NA) activity against large substrates, with activity inversely proportional to the length of the fibrous NA stalk that supports the enzymatic domain. By modulating NA stalk length in recombinant IAVs, we show that anti-stem Abs inhibit virus release from infected cells by blocking NA, accounting for their in vitro neutralization activity. NA inhibition contributes to anti-stem Ab protection in influenza-infected mice, likely due at least in part to NA-mediated inhibition of FcγR-dependent activation of innate immune cells by Ab bound to virions. Food and Drug Administration-approved NA inhibitors enhance anti-stem-based Fc-dependent immune cell activation, raising the possibility of therapeutic synergy between NA inhibitors and anti-stem mAb treatment in humans.
This is a work of the U.S. Government and is not subject to copyright protection in the United States. Foreign copyrights may apply.
PMID: 30683737 DOI: 10.1084/jem.20181624