Abstract
Recent successes with monoclonal antibody cocktails ZMappTM and MIL77 against Ebola virus (EBOV) infections have reignited interest in antibody-based therapeutics. Since the production process for monoclonal antibodies can be prolonged and costly, alternative treatments should be investigated. We produced purified equine antisera from horses hyperimmunized with EBOV virus-like particles, and tested the post-exposure efficacy of the antisera in a mouse model of infection. BALB/c mice were given up to 2 mg of purified equine antisera per animal, at 30 minutes, 1 or 2 days post-infection (dpi), in which all animals survived. To decrease the possibility of serum sickness, the equine antisera was digested with pepsin to generate F(ab′)2 fragments, with in vitro neutralizing activity comparable to whole immunoglobulin. Full protection was achieved with when treatment was initiated at 1 dpi, but the suboptimal protection observed with the 30 minute and 2 dpi groups demonstrate that in addition to virus neutralization, other Fc-dependent antibody mechanisms may also contribute to survival. Guinea pigs given 20 mg of antisera or F(ab′)2 at or starting at 1 or 2 dpi were also fully protected from EBOV infection. These results justify future efficacy studies for purified equine products in NHPs.
Highlights
Recent successes with monoclonal antibody cocktails ZMappTM and MIL77 against Ebola virus (EBOV) infections have reignited interest in antibody-based therapeutics
Immunoblotting of rBV-viral protein 40 (VP40)-GP infected Sf9 cell lysates demonstrated that the enveloped virus-like particles (eVLP) contained EBOV GP and VP40 (Supplementary Figure 2)
Three horses were immunized intramuscularly (IM) with 7 injections of eVLP over 11 weeks and the hyperimmune sera were collected from each animal at specified timepoints (Fig. 1A) to determine the serum titers by neutralization assay against a recombinant HIV-1 virus pseudotyped with EBOV GP
Summary
Recent successes with monoclonal antibody cocktails ZMappTM and MIL77 against Ebola virus (EBOV) infections have reignited interest in antibody-based therapeutics. We produced purified equine antisera from horses hyperimmunized with EBOV virus-like particles, and tested the post-exposure efficacy of the antisera in a mouse model of infection. BALB/c mice were given up to 2 mg of purified equine antisera per animal, at 30 minutes, 1 or 2 days post-infection (dpi), in which all animals survived. Guinea pigs given 20 mg of antisera or F(ab′)[2] at or starting at 1 or 2 dpi were fully protected from EBOV infection. These results justify future efficacy studies for purified equine products in NHPs. Ebola virus (EBOV) is a pathogen from the Filoviridae family, and is capable of causing severe hemorrhagic fever in humans and non-human primates. The outbreak is largely under control with no reported cases since the week of November 29th, 20155, the virus had shown itself at the peak of the outbreak to be extremely resistant to traditional containment methods designed to curb EBOV transmission
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