Development of a Cost-effective Ovine Polyclonal Antibody-Based Product, EBOTAb, to Treat Ebola Virus Infection.

Stuart David Dowall,Verena Krähling,John Landon,Emma Rayner,Roger Hewson,Irene Taylor,Miles W Carroll,Jo Callan,Ian Cameron,Thomas A Bowden,Abdulsalami Nasidi,Sarah K Fehling,Antra Zeltina,Sue Charlton,Thomas Strecker,Andrew Bosworth,Ibrahim Al-Abdulla

doi:10.1093/infdis/jiv565

Abstract

The highly glycosylated glycoprotein spike of Ebola virus (EBOV-GP1,2) is the primary target of the humoral host response. Recombinant EBOV-GP ectodomain (EBOV-GP1,2ecto) expressed in mammalian cells was used to immunize sheep and elicited a robust immune response and produced high titers of high avidity polyclonal antibodies. Investigation of the neutralizing activity of the ovine antisera in vitro revealed that it neutralized EBOV. A pool of intact ovine immunoglobulin G, herein termed EBOTAb, was prepared from the antisera and used for an in vivo guinea pig study. When EBOTAb was delivered 6 hours after challenge, all animals survived without experiencing fever or other clinical manifestations. In a second series of guinea pig studies, the administration of EBOTAb dosing was delayed for 48 or 72 hours after challenge, resulting in 100% and 75% survival, respectively. These studies illustrate the usefulness of EBOTAb in protecting against EBOV-induced disease.

Highlights

The highly glycosylated glycoprotein spike of Ebola virus (EBOV-GP1,2) is the primary target of the humoral host response
Antisera pools from sheep immunized with recombinant EBOV-GP1,2ecto exhibited strong antibody responses at week 6, which increased in blood specimens obtained on subsequent dates (Figure 2A)
EBOTAb was prepared from pools of antisera, and small-scale affinity chromatography revealed an average specificity of 10.2%

Summary

Introduction

The highly glycosylated glycoprotein spike of Ebola virus (EBOV-GP1,2) is the primary target of the humoral host response. In a second series of guinea pig studies, the administration of EBOTAb dosing was delayed for 48 or 72 hours after challenge, resulting in 100% and 75% survival, respectively. These studies illustrate the usefulness of EBOTAb in protecting against EBOV-induced disease. Several recent studies have focused on the therapeutic development of monoclonal antibodies (mAb) [4], including ZMapp, a cocktail of 3 chimeric mAb that target distinct epitopes on the EBOV glycoprotein (GP1,2) surface [5]. It was appropriate to develop an intact ovine IgG–based product for the treatment of EBOV infections

Methods

Results

Conclusion