Th213 - Therapeutic Potential of Monoclonal Antibodies Against Lymphatic Filariasis

Sean Gray – VP Research and Development, PAI Life Sciences; Darrick Carter – CEO, PAI Life Sciences; Ramaswamy Kalyanasundaram – Professor, Biomedical Sciences, University of Illinois

Abstract Text: Our laboratory developed a multivalent recombinant fusion protein vaccine, rBmHAXT, for prophylaxis against human lymphatic filariasis (LF). Seed stock of the vaccine is ready for cGMP manufacturing for phase 1 clinical trial. A consistent quality control process is essential for manufacturing the vaccine during the cGMP engineering runs to ensure that there are no batch to batch variations. We contracted with the Fred Hutchinson Cancer Center to prepare mouse B cell hybridomas against rBmHAXT. Several clones were generated. We did extensive screening on the clones and narrowed down 10 clones that produced IgG mAbs that bound to various component peptides of the rBmHAXT and showed significant binding to the native rBmHAXT. In this project, we further characterized these 10 clones for their ability to kill the infective larvae of the LF parasite (Brugia malayi) in vitro and in vivo. Our in vitro antibody-dependent cell mediated cytotoxicity assay showed that four mAbs have significant larval killing abilities in vitro (p < 0.0001). We also demonstrated the binding of these four mAbs to the larval surface and the Fc region of these mAb to the macrophages suggesting a role for macrophages in the killing of the infective larvae. These findings also confirmed that the mAbs can bind to the surface of the infective larvae. Challenge studies will demonstrate the ability of these four mAbs as therapeutic monoclonal antibodies against LF.