Development and characterization of novel chimeric monoclonal antibodies for broad spectrum neutralization of rabies virus

用于广谱中和狂犬病毒的新型嵌合单克隆抗体的开发和表征

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作者:Pan Kyeom Kim, Sun Ju Keum, Modupe O V Osinubi, Richard Franka, Ji Young Shin, Sang Tae Park, Man Su Kim, Mi Jung Park, Soo Young Lee, William Carson, Lauren Greenberg, Pengcheng Yu, Xiaoyan Tao, Wang Lihua, Qing Tang, Guodong Liang, Madhusdana Shampur, Charles E Rupprecht, Shin Jae Chang

Abstract

Current post-exposure prophylaxis for rabies virus infection has several limitations in terms of supply, cost, safety, and efficacy. Attempts to replace human or equine rabies immune globulins (HRIG or ERIG) have been made by several companies and institutes. We developed potent monoclonal antibodies to neutralize a broad spectrum of rabies viruses by screening hybridomas received from the U.S. Centers for Disease Control and Prevention (CDC). Two kinds of chimeric human antibodies (chimeric #7 and #17) were constructed by cloning the variable regions from selected hybridomas and the constant region of a human antibody. Two antibodies were bound to antigenic site III and I/IV, respectively, and were able to neutralize 51 field isolates of rabies virus that were isolated at different times and places such as Asia, Africa, North America, South America, and Australia. These two antibodies neutralize rabies viruses with high efficacy in an in vivo test using Syrian hamster and mouse models and show low risk for adverse immunogenicity.

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