Exploiting V-Gene Bias for Rapid, High-Throughput Monoclonal Antibody Isolation from Horses

Abstract

Horses and humans share a close relationship that includes both species’ viromes. Many emerging infectious diseases can be transmitted between horses and humans and can exhibit mortality rates as high as 90% in both populations. Antibody biologics represents an emerging field of rapidly discoverable and potent antiviral therapeutics. These biologics can be used to provide passive immunity, as well as blueprints for the rational design of novel active vaccine antigens. Here, we exploit the limited diversity of immunoglobulin variable genes used by horses to develop a rapid, high-throughput monoclonal antibody discovery pipeline. The antibodies isolated from two horses in this study were developed with near exclusivity from a few highly related germline genes within a single IgHV and IgλV gene family and could be recovered for cloning with just three primer pairs. This variable gene pairing was compatible with both horse and human immunoglobulin G isotypes, confirming the suitability of an equine antibody discovery pipeline for developing novel therapeutics to meet the One Health approach to infectious diseases.