Abstract
Herein we describe production of purified equine IgG obtained from horses immunized with plasmid DNA followed by boosting with Kunjin replicon virus-like particles both encoding a modified Ebola glycoprotein. Administration of the equine IgG over 5 days to cynomolgus macaques infected 24 hours previously with a lethal dose of Ebola virus suppressed viral loads by more than 5 logs and protected animals from mortality. Animals generated their own Ebola glycoprotein-specific IgG responses 9–15 days after infection, with circulating virus undetectable by day 15–17. Such equine IgG may find utility as a post-exposure prophylactic for Ebola infection and provides a low cost, scalable alternative to monoclonal antibodies, with extensive human safety data and WHO-standardized international manufacturing capability available in both high and low income countries.
Highlights
Two horses were immunized four times with 4 mg of phCMV-GP/D637L followed by a boost with 3 × 109 IU of Kunjin virus (KUN)-virus-like particle (VLP)-GP/D637L, with anti-GP antibody titers in horse serum samples (Fig. 1a) measured by enzyme-linked immunosorbent assay (ELISA)
Immunization with a KUN-VLP-GP/D637L ten weeks after the fourth DNA immunization resulted in a >20 fold increase in antibody titers, which were maintained for 13 days (Fig. 1b) when plasma was collected by plasmapheresis (Fig. 1a)
The ability of the treatment substantially to suppress the viral load is likely central to efficacy, the fall in circulating Ebola virus (EBOV) levels to undetectable levels coincided with generation by the non-human primates (NHPs) of their own immune responses to EBOV
Summary
More recent IgG studies have shown post-exposure protection in guinea pigs (using challenge with guinea pig-adapted EBOV) using (i) IgG from horses and pigs immunized with EBOV virus-like particles[15,16], and (ii) serum from sheep immunized with recombinant GP17. These IgG products have not, to our knowledge, proceeded to NHP studies. We have previously demonstrated high immunogenicity of Kunjin virus (KUN) replicon-based vectors in horses[18] and have shown protective efficacy of a KUN replicon virus-like particle (VLP)-based vaccine (KUN-VLP-GP/D637L) against lethal EBOV challenge in guinea pigs[19] and NHPs20. We further show that post exposure treatment with this equine IgG protects NHPs from lethal EBOV infection
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