tetano
Editor, Senior Moderator
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J Clin Virol. 2018 Sep 26;108:105-111. doi: 10.1016/j.jcv.2018.09.016. [Epub ahead of print]
[h=1]Differences in the ease with which mutant viruses escape from human monoclonal antibodies against the HA stem of influenza A virus.[/h] Yamayoshi S[SUP]1[/SUP], Yasuhara A[SUP]1[/SUP], Ito M[SUP]1[/SUP], Uraki R[SUP]1[/SUP], Kawaoka Y[SUP]2[/SUP].
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[h=3]Abstract[/h] [h=4]BACKGROUND:[/h] Broadly protective human monoclonal antibodies that recognize the conserved epitopes in the HA of influenza A virus are being developed as therapeutic agents. Emergence of resistant viruses must always be considered when developing therapeutic agents against influenza.
[h=4]OBJECTIVES:[/h] We examined human hetero-reactive mAbs against the HA stem of influenza A virus for the ease with which escape mutant viruses emerged.
[h=4]STUDY DESIGN:[/h] We attempted to generate the mutant viruses escaped from the hetero-reactive anti-HA stem antibodies. We also evaluated their protective efficacy, binding affinity, and epitopes.
[h=4]RESULTS:[/h] We obtained several human monoclonal antibodies (mAbs) that react with the HA of different HA subtypes of influenza A virus belonging to group 1. Upon attempting to generate escape mutant viruses, we found that the ease with which such viruses emerged differed among the mAbs; viruses barely escaped from two of the mAbs (clones S9-3-37 and F20C77), whereas escape from the third mAb (clone F5B7) occurred readily. Comparisons of the mAbs revealed that the HA stem epitopes, in vitro neutralization potency, binding affinity to H1-HA, and protective efficacy against lethal challenge with H1N1pdm09 virus were all comparable.
[h=4]CONCLUSIONS:[/h] These results demonstrate the importance of determining the ease with which escape mutant viruses emerge when evaluating anti-HA stem antibodies as antiviral agents during preclinical testing.
Copyright ? 2018 Elsevier B.V. All rights reserved.
[h=4]KEYWORDS:[/h] Escape mutant virus; HA stem; Human monoclonal antibody; Influenza A virus
PMID: 30292135 DOI: 10.1016/j.jcv.2018.09.016
J Clin Virol. 2018 Sep 26;108:105-111. doi: 10.1016/j.jcv.2018.09.016. [Epub ahead of print]
[h=1]Differences in the ease with which mutant viruses escape from human monoclonal antibodies against the HA stem of influenza A virus.[/h] Yamayoshi S[SUP]1[/SUP], Yasuhara A[SUP]1[/SUP], Ito M[SUP]1[/SUP], Uraki R[SUP]1[/SUP], Kawaoka Y[SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] [h=4]BACKGROUND:[/h] Broadly protective human monoclonal antibodies that recognize the conserved epitopes in the HA of influenza A virus are being developed as therapeutic agents. Emergence of resistant viruses must always be considered when developing therapeutic agents against influenza.
[h=4]OBJECTIVES:[/h] We examined human hetero-reactive mAbs against the HA stem of influenza A virus for the ease with which escape mutant viruses emerged.
[h=4]STUDY DESIGN:[/h] We attempted to generate the mutant viruses escaped from the hetero-reactive anti-HA stem antibodies. We also evaluated their protective efficacy, binding affinity, and epitopes.
[h=4]RESULTS:[/h] We obtained several human monoclonal antibodies (mAbs) that react with the HA of different HA subtypes of influenza A virus belonging to group 1. Upon attempting to generate escape mutant viruses, we found that the ease with which such viruses emerged differed among the mAbs; viruses barely escaped from two of the mAbs (clones S9-3-37 and F20C77), whereas escape from the third mAb (clone F5B7) occurred readily. Comparisons of the mAbs revealed that the HA stem epitopes, in vitro neutralization potency, binding affinity to H1-HA, and protective efficacy against lethal challenge with H1N1pdm09 virus were all comparable.
[h=4]CONCLUSIONS:[/h] These results demonstrate the importance of determining the ease with which escape mutant viruses emerge when evaluating anti-HA stem antibodies as antiviral agents during preclinical testing.
Copyright ? 2018 Elsevier B.V. All rights reserved.
[h=4]KEYWORDS:[/h] Escape mutant virus; HA stem; Human monoclonal antibody; Influenza A virus
PMID: 30292135 DOI: 10.1016/j.jcv.2018.09.016