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Generation of a protective murine monoclonal antibody against the stem of influenza hemagglutinins from group 1 viruses and identification of resistan

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Editor, Senior Moderator
PLoS One. 2019 Sep 12;14(9):e0222436. doi: 10.1371/journal.pone.0222436. eCollection 2019.
[h=1]Generation of a protective murine monoclonal antibody against the stem of influenza hemagglutinins from group 1 viruses and identification of resistance mutations against it.[/h] Wang W[SUP]1[/SUP], Vassell R[SUP]1[/SUP], Song HS[SUP]1[/SUP], Chen Q[SUP]1[/SUP], Keller PW[SUP]1[/SUP], Verma S[SUP]1[/SUP], Alvarado-Facundo E[SUP]1[/SUP], Wan H[SUP]1[/SUP], Schmeisser F[SUP]1[/SUP], Meseda CA[SUP]1[/SUP], Weir JP[SUP]1[/SUP], Weiss CD[SUP]1[/SUP].
[h=3]Author information[/h] 1 Division of Viral Products, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, United States of America.

[h=3]Abstract[/h] Vaccines that elicit broadly cross-neutralizing antibodies, including antibodies that target the conserved stem of hemagglutinin (HA), are being developed as a strategy for next-generation influenza vaccines that protect against influenza across multiple years. However, efficient induction of cross-neutralizing antibodies remains a challenge, and potential escape mutations have not been well characterized. Here we elicited cross-neutralizing antibodies by immunizing animals with the hemagglutinins from H5 and H9 subtype influenza A viruses that are sensitive to neutralization by stem antibodies. We further isolated and characterized an HA stem monoclonal antibody 4C2 that broadly neutralizes group 1 influenza viruses and identified HA mutations that reduced sensitivity to stem antibodies. Our results offer insights for next-generation influenza vaccine strategies for inducing cross-neutralizing antibodies.


PMID: 31513662 DOI: 10.1371/journal.pone.0222436
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