title: Antibody-dependent-cellular-cytotoxicity-inducing antibodies significantly affect the post-exposure treatment of Ebola virus infection.
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.
authors.affiliation: Division of HIV/AIDS and Sex-transmitted Virus Vaccines, National Institutes for Food and Drug Control, Beijing 100050, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Division of Animal Model Research, Institute for Laboratory Animal Resources, National Institutes for Food and Drug Control, Beijing 100050, China.
authors.forename: Changfa
authors.initials: C
authors.lastname: Fan
authors.affiliation: Division of HIV/AIDS and Sex-transmitted Virus Vaccines, National Institutes for Food and Drug Control, Beijing 100050, China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Li
authors.affiliation: Division of Animal Model Research, Institute for Laboratory Animal Resources, National Institutes for Food and Drug Control, Beijing 100050, China.
authors.forename: Shuya
authors.initials: S
authors.lastname: Zhou
authors.affiliation: Division of HIV/AIDS and Sex-transmitted Virus Vaccines, National Institutes for Food and Drug Control, Beijing 100050, China.
authors.forename: Weijin
authors.initials: W
authors.lastname: Huang
authors.affiliation: Division of Monoclonal Antibody, National Institutes for Food and Drug Control, Beijing 100050, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Wang
authors.affiliation: Sino Biological Inc., Beijing 100176, China.
authors.forename: Chunyun
authors.initials: C
authors.lastname: Sun
authors.affiliation: Division of HIV/AIDS and Sex-transmitted Virus Vaccines, National Institutes for Food and Drug Control, Beijing 100050, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Wang
authors.affiliation: Division of Animal Model Research, Institute for Laboratory Animal Resources, National Institutes for Food and Drug Control, Beijing 100050, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Wu
authors.affiliation: Division of HIV/AIDS and Sex-transmitted Virus Vaccines, National Institutes for Food and Drug Control, Beijing 100050, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Ma
authors.affiliation: Division of Animal Model Research, Institute for Laboratory Animal Resources, National Institutes for Food and Drug Control, Beijing 100050, China.
authors.forename: Baowen
authors.initials: B
authors.lastname: Li
authors.affiliation: Sino Biological Inc., Beijing 100176, China.
authors.forename: Liangzhi
authors.initials: L
authors.lastname: Xie
authors.affiliation: Division of HIV/AIDS and Sex-transmitted Virus Vaccines, National Institutes for Food and Drug Control, Beijing 100050, China.
authors.forename: Youchun
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000276:immunology*; D057134:Antibodies, Neutralizing / Q000008:administration & dosage; D000914:Antibodies, Viral / Q000008:administration & dosage; D000920:Antibody-Dependent Cell Cytotoxicity; D004195:Disease Models, Animal; D005260:Female; D019142:Hemorrhagic Fever, Ebola / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral