IDENTIFICATION AND CHARACTERIZATION OF HUMAN THERAPEUTIC ANTIBODY CANDIDATES FOR DENV4

Abstract

Dengue Virus is an arthropod-borne flavivirus that poses a great threat to human populations. Among these four related, but antigenically distinct serotypes, DENV4 is the rarest and most poorly defined form of Dengue. Currently, no specific anti-viral treatment is available. Durable long-term immunity to dengue is mediated by serotype-specific antibodies. Hence, serotype-specific human monoclonal antibodies represent candidate therapeutic molecules for DENV. In this project, advanced human antibody discovery and protein engineering methodologies are employed to isolate, express and characterize neutralizing antibodies from convalescent dengue patient blood samples. One human derived dengue serotype-4 specific monoclonal antibody was identified and expressed. Its anti-viral efficacy and binding pattern were studied through a series of functional in vitro/ in vivo assays. This antibody represents a good therapeutic candidate considering its strong neutralizing potency, and the study on it also provides some understanding of dengue neutralizing mechanism.