Human monoclonal single-chain antibodies specific to dengue virus envelope protein

Abstract

Dengue virus (DENV) infection is an arthropod-borne disease with increasing prevalence worldwide. Attempts have been made to develop therapeutic molecules for treatment for DENV infection. However, most of potentially therapeutic DENV monoclonal antibody was originated from mouse, which could cause undesirable effects in human recipients. Thus, fully human antibody is preferable for therapeutic development. Human single-chain variable fragments (HuScFv) with inhibitory effect to DENV infection were generated in this study. HuScFv molecules were screened and selected from the human antibody phage display library by using purified recombinant DENV full-length envelope (FL-E) and its domain III (EDIII) proteins as target antigens for biopanning. HuScFv molecules were then tested for their bindings to DENV particles by indirect ELISA and immunofluorescent microscopy. EDIII-specific HuScFv exhibited neutralizing effect to DENV infection in Vero cells in a dose-dependent manner as determined by plaque formation and cell ELISA. Epitope mapping and molecular docking results concordantly revealed interaction of HuScFv to functional loop structure in EDIII of the DENV E protein. The neutralizing HuScFv molecule warrants further development as a therapeutic biomolecule for DENV infection. © 2013 The Society for Applied Microbiology.