Structure-Guided Design of an Anti-dengue Antibody Directed to a Non-immunodominant Epitope.

ABSTRACT: Dengue is the most common vector-borne viral disease, causing nearly 400 million infections yearly. Currently there are no approved therapies. Antibody epitopes that elicit weak humoral responses may not be accessible by conventional B cell panning methods. To demonstrate an alternative strategy to generating a therapeutic antibody, we employed a non-immunodominant, but functionally relevant, epitope in domain III of the E protein, and engineered by structure-guided methods an antibody directed to it. The resulting antibody, Ab513, exhibits high-affinity binding to, and broadly neutralizes, multiple genotypes within all four serotypes. To assess therapeutic relevance of Ab513, activity against important human clinical features of dengue was investigated. Ab513 mitigates thrombocytopenia in

SUBMITTER: Robinson LN 

PROVIDER: S-EPMC4758460 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature