Post-exposure treatment of Ebola virus disease in guinea pigs using EBOTAb, an ovine antibody-based therapeutic

Abstract

Ebola virus (EBOV) is highly pathogenic, with a predisposition to cause outbreaks in human populations accompanied by significant mortality. An ovine polyclonal antibody therapy has been developed against EBOV, named EBOTAb. When tested in the stringent guinea pig model of EBOV disease, EBOTAb has been shown to confer protection at levels of 83.3%, 50% and 33.3% when treatment was first started on days 3, 4 and 5 post-challenge, respectively. These timepoints of when EBOTAb treatment was initiated correspond to when levels of EBOV are detectable in the circulation and thus mimic when treatment would likely be initiated in human infection. The effects of EBOTAb were compared with those of a monoclonal antibody cocktail, ZMapp, when delivered on day 3 post-challenge. Results showed ZMapp to confer complete protection against lethal EBOV challenge in the guinea pig model at this timepoint. The data reported demonstrate that EBOTAb is an effective treatment against EBOV disease, even when delivered late after infection.

Post-exposure treatment of non-human primates lethally infected with Ebola virus with EBOTAb, a purified ovine IgG product

“…This data supports the results reported showing efficacy of EBOTAb in the guinea pig model of EBOV disease 27, 28, 55 . Clearly pAb treatment of EBOV has some advantages over mAb-based therapies.…”

“…In response to the 2014 West Africa EBOV outbreak, an ovine immunoglobulin preparation was rapidly developed, termed EBOTAb, which demonstrated neutralisation activity and exhibited promising results in the EBOV guinea pig model 27 , 28 . Due to the outbred guinea pig model of EBOV infection showing coagulopathy 29 , this model is regarded as a more authentic model of human disease than mice or inbred guinea pig models and an important animal system 30 .…”

Generation of therapeutic antisera for emerging viral infections

“…Even though immunization of horses with inactivated EBOV failed to produce effective therapeutic antisera, 28 more recent approaches using adjuvanted recombinant EBOV-GP ectodomain for immunization of sheep led to antisera that were effective as post-exposure treatment of rodents. 52 , 53 The production of fully human polyclonal antibodies by immunization of transchromosomal cattle with EBOV-GP nanoparticles constitutes a further important step, 54 but may be limited by availability of these transgenic animals. By comparing the replication-competent recombinant VSV and the replication-incompetent MVA vaccine platforms with adjuvanted VLPs, we show that even though de novo antigen expression was associated with an earlier development of total anti-EBOV antibodies, functional titers increased over the course of the immunizations for all candidates, with adjuvanted VLPs resulting in induction of similar final titers as VSVΔG/EBOV-GP.…”

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

“…Several passive immunotherapeutics are under development to treat emerging infectious diseases and filoviruses [1][2][3][4][5][6]. However, traditional human-derived and heterologous animal-derived polyclonal immunoglobulins (Igs) and monoclonal antibodies can have lengthy development and/or clinical safety issues [1,7,8].…”