Engineering a novel IgG-like bispecific antibody against enterovirus A71

Hsiang Ching Wang, Hui Chen Hung, Peng Nien Huang, Yu An Kung, Sung Nien Tseng, Yun Ming Wang, Shin Ru Shih, John Tsu-An Hsu*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Frequent outbreaks of enterovirus A71 (EVA71) occur in the Asia-Pacific area, and these are closely associated with severe neurological symptoms in young children. No effective antiviral therapy is currently available for the treatment of EVA71 infection. The development of monoclonal antibodies (mAbs) has demonstrated promise as a novel therapy for the prevention and treatment of infectious diseases. Several medical conditions have been treated using bispecific or multi-specific antibodies that recognize two or more distinct epitopes simultaneously. However, bispecific or multi-specific antibodies often encounter protein expression and product stability problems. In this study, we developed an IgG-like bispecific antibody (E18-F1) comprising two anti-EVA71 antibodies: E18 mAb and llama-derived F1 single-domain antibody. E18-F1 was demonstrated to exhibit superior binding affinity and antiviral activity compared with E18 or F1. Additionally, E18-F1 not only improved survival rate, but also reduced clinical signs in human SCARB2 receptor (hSCARB2) transgenic mice challenged with a lethal dose of EVA71. Altogether, our results reveal that E18-F1 is a simple format bispecific antibody with promising antiviral activity for EVA71.

    Original languageEnglish
    Article number100860
    JournalBiochemistry and Biophysics Reports
    Volume24
    DOIs
    StatePublished - Dec 2020

    Keywords

    • Antiviral drug
    • Bispecific antibody
    • Enterovirus A71
    • Single-domain antibody

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