In vitro and in vivo neutralization of Dengue virus by a single domain antibody

Abstract

To alleviate the contribution of antibody dependent enhancement in DenV pathogenesis, we obtain a DenV neutralizing single domain antibody (sdAb) from an in-house constructed phage display library of camelid VHH. The anti-DenV sdAb specifically reacts with the envelope (E) protein of DenV with a Kd value of 2x108. Molecular dynamic simulations and docking analysis show that the sdAb interacts with the DenV(E) protein via domain II (EDII) and interferes with the virus internalization process. The anti-DenV(E) sdAb potently inhibits the infectivity of a DenV(E) protein expressing pseudovirus as well as that of a virulent DenV in vitro. A mouse adapted DenV2 induces 100% mortality in the infected IFNRKO mice, but the animals injected with the sdAb neutralized virus remain fully protected. Furthermore, the therapeutically administered anti-DenV(E) sdAb slows down the disease progression and enhances the survival of DenV infected animals. In conclusion, we report an anti-DenV(E) sdAb as a potential therapy to manage DenV pathogenesis.