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Generation and characterization of neutralizing human recombinant antibodies against antigenic site II of rabies virus glycoprotein

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Abstract

The currently recommended treatment for individuals exposed to rabies virus (RV) is post-exposure prophylaxis (PEP) through the combined administration of rabies vaccine and rabies immune globulin (RIG). Human monoclonal antibodies (mAbs) that neutralize RV offer an opportunity to replace RIG for rabies PEP. Here, a combinatorial human Fab library was constructed using antibody genes derived from the blood of RV-vaccinated donors. Selections of this library against purified RV virions resulted in the identification of 11 unique Fab antibodies specific for RV glycoprotein. Of the Fab antibodies, five were converted to full human IgG1 format. The human IgG antibodies revealed high binding affinity and neutralizing activities against RV fixed strains through a rapid fluorescent focus inhibition test in vitro as well as the early stage protective function after exposure to RV infection in vivo. Furthermore, epitope mapping and binding competition analysis showed that all of obtained human neutralizing and protective antibodies were directed to the antigenic site II of RV glycoprotein. Our results provide not only important insight into the protective immune response to RV in humans, but also more candidates eligible for use in a mAb cocktail aimed at replacing RIG for rabies post-exposure prophylaxis.

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Acknowledgments

This work was mainly supported by 863 Project (2009AA02Z109) from the Ministry of Science and Technology of the People’s Republic of China. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. No additional external funding received for this study.

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Authors and Affiliations

  1. National Institute for Viral Disease Control and Prevention, China CDC, Beijing, 102206, China

    Lina Sun, Zhe Chen, Li Yu, Chuan Li, Jing Jin, Xinxin Shen, Xinjun Lv, Qing Tang, Dexin Li & Mifang Liang

  2. New Drug R&D Center, State Key Laboratory of Development of Antibody Drugs, North China Pharmaceutical Corporation, Shijiazhuang, Hebei, China

    Jingshuang Wei

Authors
  1. Lina Sun
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  2. Zhe Chen
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  3. Li Yu
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  4. Jingshuang Wei
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  5. Chuan Li
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  6. Jing Jin
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  7. Xinxin Shen
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  8. Xinjun Lv
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  9. Qing Tang
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  10. Dexin Li
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  11. Mifang Liang
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Correspondence to Mifang Liang.

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Sun, L., Chen, Z., Yu, L. et al. Generation and characterization of neutralizing human recombinant antibodies against antigenic site II of rabies virus glycoprotein. Appl Microbiol Biotechnol 96, 357–366 (2012). https://doi.org/10.1007/s00253-012-4171-4

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  • DOI: https://doi.org/10.1007/s00253-012-4171-4

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