ABSTRACT
Ebola virus (EBOV) remains one of the most lethal transmissible infections and is responsible for high fatality rates and substantial morbidity during sporadic outbreaks. With increasing human incursions into endemic regions and the reported possibility of airborne transmission, EBOV is a high-priority public health threat for which no preventive or therapeutic options are currently available. Recent studies have demonstrated that cocktails of monoclonal antibodies are effective at preventing morbidity and mortality in nonhuman primates (NHPs) when administered as a post-exposure prophylactic within 1 or 2 days of challenge. To test whether one of these cocktails (MB-003) demonstrates efficacy as a therapeutic (after the onset of symptoms), we challenged NHPs with EBOV and initiated treatment upon confirmation of infection according to a diagnostic protocol for U.S. Food and Drug Administration Emergency Use Authorization and observation of a documented fever. Of the treated animals, 43% survived challenge, whereas both the controls and all historical controls with the same challenge stock succumbed to infection. These results represent successful therapy of EBOV infection in NHPs.
Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Viral/therapeutic use , Ebola Vaccines/therapeutic use , Ebolavirus/immunology , Hemorrhagic Fever, Ebola/therapy , Animals , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Viral/administration & dosage , Disease Models, Animal , Ebola Vaccines/administration & dosage , Ebolavirus/genetics , Female , Hemorrhagic Fever, Ebola/immunology , Hemorrhagic Fever, Ebola/prevention & control , Humans , Macaca mulatta , Male , Plantibodies/administration & dosage , Plantibodies/therapeutic use , Post-Exposure Prophylaxis/methods , Translational Research, Biomedical , Viremia/immunology , Viremia/prevention & control , Viremia/therapyABSTRACT
Filovirus infections can cause a severe and often fatal disease in humans and nonhuman primates, including great apes. Here, three anti-Ebola virus mouse/human chimeric mAbs (c13C6, h-13F6, and c6D8) were produced in Chinese hamster ovary and in whole plant (Nicotiana benthamiana) cells. In pilot experiments testing a mixture of the three mAbs (MB-003), we found that MB-003 produced in both manufacturing systems protected rhesus macaques from lethal challenge when administered 1 h postinfection. In a pivotal follow-up experiment, we found significant protection (P < 0.05) when MB-003 treatment began 24 or 48 h postinfection (four of six survived vs. zero of two controls). In all experiments, surviving animals that received MB-003 experienced little to no viremia and had few, if any, of the clinical symptoms observed in the controls. The results represent successful postexposure in vivo efficacy by a mAb mixture and suggest that this immunoprotectant should be further pursued as a postexposure and potential therapeutic for Ebola virus exposure.
