Onchocerca volvulus is a filarial parasite transmitted to humans by female Simulium spp. black flies. Infection with this parasite can cause blindness and severe skin disease among humans in Africa and the Americas. Enzyme-linked Immunosorbent Assay serological testing of OV-16 antigen is a diagnostic tool for determining effective elimination of the parasite. Programs typically rely on OV–16 ELISA to evaluate the progress towards interruption and/or elimination of disease by mass drug distribution of ivermectin and vector larvicidal control efforts. As elimination grows closer, monoclonal antibody positive controls for OV-16 ELISA become important to develop for Onchocerca testing due to the limited availability of pooled sera positive controls. Recent evaluation of laboratory designed OV-16 ELISA coating antigen by the Unnasch Lab (University of South Florida) showed that polymorphisms occurred which may alter the ability of the humanized monoclonal antibody to recognize the cognate antigen. With this development, it was important to evaluate these polymorphisms and isolate them for further testing against the standardized monoclonal antibody and positive sera to determine the effects antigenic polymorphisms could have on diagnostic testing. Upon evaluation, the polymorphisms did influence signaling when testing the monoclonal antibody. However, little effect on the recognition of the antigen was seen when different isoforms were evaluated against sera from O. volvulus infected individuals. Data suggest that the epitope recognized by the synthetically produced monoclonal antibody is not immuno-dominant in infected individuals.