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.

Fully Human Immunoglobulin G From Transchromosomic Bovines Treats Nonhuman Primates Infected With Ebola Virus Makona Isolate

“…Natural killer cells only express Fcγ-RIIIA, and, similar to ADNP, activated NK cells degranulate (CD107a expression) [41,42] and produce cytokines IFN-γ and the chemokine MIP-1β to induce ADCC of infected cells. A growing body of evidence suggests that ADCC may contribute to the efficacy of some monoclonal antibodies against EBOV [43][44][45], and both NK cells and monocytes have been implicated in protection against EBOV [46,47] disease in NHP models.…”

Establishment and validation of a pseudovirus neutralization assay for SARS-CoV-2

“…To avoid dealing with infectious virus, we have developed a series of pseudovirus-based neutralization assays (PBNAs) for emerging and re-emerging viruses, including MERS-CoV [12], rabies virus [13], Ebola virus [14], Marburg virus [15], Lassa virus [16], Chikungunya virus [17], Nipah virus [18], Rift valley virus [19], and others. In this communication, we developed a PBNA for evaluation of anti-viral measures for SARS-CoV-2, which would be used to evaluate the inhibition of viral attachment and entry mediated by the S protein.…”

Rabies-based vaccine induces potent immune responses against Nipah virus

“…In antiviral defense, Th1-type antibodies are known to participate in nonneutralizing effector functions, such as NK cell-mediated antibody dependent cytotoxicity (ADCC) or macrophage/monocytemediated antibody dependent cellular phagocytosis (ADCP). [46][47][48][49] It is possible that these other mechanisms contribute to vaccineinduced protection with INAC NIPARAB in addition to classic neutralization.…”