Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology · 2018
Differences in the ease with which mutant viruses escape from human monoclonal antibodies against the HA stem of influenza A virus.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Yamayoshi Seiya, Yasuhara Atsuhiro, Ito Mutsumi, Uraki Ryuta, Kawaoka Yoshihiro
Аннотация
BACKGROUND: 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.
OBJECTIVES: We examined human hetero-reactive mAbs against the HA stem of influenza A virus for the ease with which escape mutant viruses emerged.
STUDY DESIGN: 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.
RESULTS: 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.
CONCLUSIONS: 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.
OBJECTIVES: We examined human hetero-reactive mAbs against the HA stem of influenza A virus for the ease with which escape mutant viruses emerged.
STUDY DESIGN: 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.
RESULTS: 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.
CONCLUSIONS: 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.