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Antibody-dependent-cellular-cytotoxicity-inducing antibodies significantly affect the post-exposure treatment of Ebola virus infection.

Antibody-dependent-cellular-cytotoxicity-inducing antibodies significantly affect the post-exposure treatment of Ebola virus infection.
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Liu Q, Fan C, Li Q, Zhou S, Huang W, Wang L, Sun C, Wang M, Wu X, Ma J, Li B, Xie L, Wang Y,


Liu Q, Fan C, Li Q, Zhou S, Huang W, Wang L, Sun C, Wang M, Wu X, Ma J, Li B, Xie L, Wang Y, (click to view)

Liu Q, Fan C, Li Q, Zhou S, Huang W, Wang L, Sun C, Wang M, Wu X, Ma J, Li B, Xie L, Wang Y,

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Scientific reports 2017 03 307() 45552 doi 10.1038/srep45552

Abstract

Passive immunotherapy with monoclonal antibodies (mAbs) is an efficacious treatment for Ebola virus (EBOV) infections in animal models and humans. Understanding what constitutes a protective response is critical for the development of novel therapeutic strategies. We generated an EBOV-glycoprotein-pseudotyped Human immunodeficiency virus to develop sensitive neutralizing and antibody-dependent cellular cytotoxicity (ADCC) assays as well as a bioluminescent-imaging-based mouse infection model that does not require biosafety level 4 containment. The in vivo treatment efficiencies of three novel anti-EBOV mAbs at 12 h post-infection correlated with their in vitro anti-EBOV ADCC activities, without neutralizing activity. When they were treated with these mAbs, natural killer cell (NK)-deficient mice had lower viral clearance than WT mice, indicating that the anti-EBOV mechanism of the ADCC activity of these mAbs is predominantly mediated by NK cells. One potent anti-EBOV mAb (M318) displayed unprecedented neutralizing and ADCC activities (neutralization IC50, 0.018 μg/ml; ADCC EC50, 0.095 μg/ml). These results have important implications for the efficacy of antiviral drugs and vaccines as well as for pathogenicity studies of EBOV.

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