Please use this identifier to cite or link to this item: https://doi.org/10.1080/22221751.2019.1708215
Title: Contribution of Fc-dependent cell-mediated activity of a vestigial esterase-targeting antibody against H5N6 virus infection
Authors: Zheng, Zhiqiang 
Teo, Su Hui Catherine 
Arularasu, Suganya Cheyyatraivendran 
Liu, Zhehao 
Mohd-Ismail, Nur Khairiah 
Mok, Chee Keng 
Ong, Chee Bing
Chu, Justin Jang-hann 
Tan, Yee-Joo 
Keywords: Science & Technology
Life Sciences & Biomedicine
Immunology
Microbiology
Influenza A virus
Antibody-dependent cellular cytotoxicity
Complement dependent cytotoxicity
Antibody-dependent cellular phagocytosis
Vestigial esterase domain
INFLUENZA-VIRUS
MONOCLONAL-ANTIBODY
GAMMA-RI
NEUTRALIZING ANTIBODY
DOMESTIC DUCKS
C(H)2 DOMAIN
HUMAN IGG1
REASSORTANT
PROTECTION
BINDING
Issue Date: 1-Jan-2020
Publisher: TAYLOR & FRANCIS LTD
Citation: Zheng, Zhiqiang, Teo, Su Hui Catherine, Arularasu, Suganya Cheyyatraivendran, Liu, Zhehao, Mohd-Ismail, Nur Khairiah, Mok, Chee Keng, Ong, Chee Bing, Chu, Justin Jang-hann, Tan, Yee-Joo (2020-01-01). Contribution of Fc-dependent cell-mediated activity of a vestigial esterase-targeting antibody against H5N6 virus infection. EMERGING MICROBES & INFECTIONS 9 (1) : 95-110. ScholarBank@NUS Repository. https://doi.org/10.1080/22221751.2019.1708215
Abstract: © 2020, © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group, on behalf of Shanghai Shangyixun Cultural Communication Co., Ltd. The highly pathogenic avian influenza A (H5N6) virus has caused sporadic human infections with a high case fatality rate. Due to the continuous evolution of this virus subtype and its ability to transmit to humans, there is an urgent need to develop effective antiviral therapeutics. In this study, a murine monoclonal antibody 9F4 was shown to display broad binding affinity against H5Nx viruses. Furthermore, 9F4 can neutralize H5N6 pseudotyped particles and prevent entry into host cells. Additionally, ADCC/ADCP deficient L234A, L235A (LALA) and CDC deficient K322A mutants were generated and displayed comparable binding affinity and neutralizing activity as wild type 9F4 (9F4-WT). Notably, 9F4-WT, 9F4-LALA and 9F4-K322A exhibit in vivo protective efficacies against H5N6 infections in that they were able to reduce viral loads in mice. However, only 9F4-WT and 9F4-K322A but not 9F4-LALA were able to reduce viral pathogenesis in H5N6 challenged mice. Furthermore, depletion of phagocytic cells in mice lungs nullifies 9F4-WT's protection against H5N6 infections, suggesting a crucial role of the host's immune cells in 9F4 antiviral activity. Collectively, these findings reveal the importance of ADCC/ADCP function for 9F4-WT protection against HPAIV H5N6 and demonstrate the potential of 9F4 to confer protection against the reassortant H5-subtype HPAIVs.
Source Title: EMERGING MICROBES & INFECTIONS
URI: https://scholarbank.nus.edu.sg/handle/10635/170663
ISSN: 22221751
DOI: 10.1080/22221751.2019.1708215
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