Generation of antibodies towards dengue nonstructural protein 5 using phage display.

Abstract

Dengue virus (DENV) is the causative agent of dengue infections worldwide, for which no vaccines or antiviral drugs are available at present. The bifunctional nonstructural protein 5 (NS5) is an attractive target for the development of antibodies since it is integral to the replication complex and essential for DENV replication. In this study, the two functional domains of NS5- methytransferase (MTase) and RNA-dependent RNA polymerase (RdRp) were used as antigens in a multiplex biopanning approach with naïve human Fab-phage display library. Five unique Fab-phage clones were identified; 3 bound to only the RdRp domain, one bound to only the MTase domain and another bound to both domains. These Fab-antibodies have many applications: they are valuable tools that can enable deeper understanding of DENV replication; they are important to drug discovery efforts; and they are potential therapeutics.