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Citation: Rui Wang, Haiwei Zhang, Cheng Peng, Jian Shi, Huajun Zhang, Rui Gong. Identification and Characterization of a Novel Single Domain Antibody Against Ebola Virus [J].VIROLOGICA SINICA, 2021, 36(6) : 1600-1610.  http://dx.doi.org/10.1007/s12250-021-00454-z

Identification and Characterization of a Novel Single Domain Antibody Against Ebola Virus

  • Corresponding author: Huajun Zhang, hjzhang@wh.iov.cn, ORCID: http://orcid.org/0000-0001-8161-3949
    Rui Gong, gongr@wh.iov.cn, ORCID: http://orcid.org/0000-0001-9222-5642
  • Received Date: 05 June 2021
    Accepted Date: 09 August 2021
    Published Date: 11 October 2021
    Available online: 01 December 2021
  • Ebola virus (EBOV) belongs to the Filoviridae family and causes severe illnesses such as hemorrhagic fever with a high mortality rate up to 90%. Now two antibody drugs termed Inmazeb and Ebanga have been approved for treating EBOV infection. However, clinical studies have demonstrated that the mortality rate of the patients who received these two antibody drugs remains above 30%. Therefore, novel therapeutics with better efficacy is still desired. The isolated human IgG1 constant domain 2 (CH2 domain) has been proposed as a scaffold for the development of C-based single domain antibodies (C-sdAbs) as therapeutic candidates against viral infections and other diseases. Here, we screened and identified a novel C-sdAb termed M24 that targets EBOV glycoprotein (GP) from a C-sdAb phage display library. M24 neutralizes the pseudotype EBOV with IC50 of 0.8 nmol/L (12 ng/mL) and has modest neutralizing activity against authentic EBOV. Epitope determination, including molecular docking and site mutation analysis, discloses that M24 binds to the internal fusion loop (IFL) within GP2, a transmembrane subunit of GP. Interestingly, we found that the binding of M24 to GP at pH 5.5 has dramatically decreased compared to the binding at pH 7.5, which may lead to weak efficacy in the neutralization of authentic EBOV. Since no sdAb against EBOV infection has been reported to date, our results not only give a proof of concept that sdAbs could be utilized for the development of potential therapeutic candidates against EBOV infection, but also provide useful information for the discovery and improvement of anti-EBOV agents.


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    Identification and Characterization of a Novel Single Domain Antibody Against Ebola Virus

      Corresponding author: Huajun Zhang, hjzhang@wh.iov.cn
      Corresponding author: Rui Gong, gongr@wh.iov.cn
    • 1. CAS Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, 430071, China
    • 2. University of Chinese Academy of Sciences, Beijing, 100049, China

    Abstract: 

    Ebola virus (EBOV) belongs to the Filoviridae family and causes severe illnesses such as hemorrhagic fever with a high mortality rate up to 90%. Now two antibody drugs termed Inmazeb and Ebanga have been approved for treating EBOV infection. However, clinical studies have demonstrated that the mortality rate of the patients who received these two antibody drugs remains above 30%. Therefore, novel therapeutics with better efficacy is still desired. The isolated human IgG1 constant domain 2 (CH2 domain) has been proposed as a scaffold for the development of C-based single domain antibodies (C-sdAbs) as therapeutic candidates against viral infections and other diseases. Here, we screened and identified a novel C-sdAb termed M24 that targets EBOV glycoprotein (GP) from a C-sdAb phage display library. M24 neutralizes the pseudotype EBOV with IC50 of 0.8 nmol/L (12 ng/mL) and has modest neutralizing activity against authentic EBOV. Epitope determination, including molecular docking and site mutation analysis, discloses that M24 binds to the internal fusion loop (IFL) within GP2, a transmembrane subunit of GP. Interestingly, we found that the binding of M24 to GP at pH 5.5 has dramatically decreased compared to the binding at pH 7.5, which may lead to weak efficacy in the neutralization of authentic EBOV. Since no sdAb against EBOV infection has been reported to date, our results not only give a proof of concept that sdAbs could be utilized for the development of potential therapeutic candidates against EBOV infection, but also provide useful information for the discovery and improvement of anti-EBOV agents.