Redesign of a cross-reactive antibody to dengue virus with broad-spectrum activity and increased in vivo potency

Dengue virus infects more than 200 million people each year, and incidence of severe disease is increasing with no effective countermeasures. We demonstrate in this paper the engineering of an antibody that binds to all four serotypes of dengue virus with potent activity in vitro and in vivo. We also outline a distinct and widely applicable approach to antibody engineering that provides important information on the paratope/epitope interface in the absence of crystal structure data, enabling identification of antibody amino acids that could be mutated. We demonstrate experimentally the alteration of both specificity (enabling cross-serotype binding) and affinity of the engineered antibody.