Therapeutic Efficacy of Antibodies Lacking FcγR against Lethal Dengue Virus Infection Is Due to Neutralizing Potency and Blocking of Enhancing Antibodies

Dengue hemorrhagic fever and dengue shock syndrome (dhf/dss) are life-threatening complications following infection with one of the four serotypes of dengue virus (denv). at present,no vaccine or antiviral therapies are available against dengue. here,we characterized a panel of eight human or mouse-human chimeric monoclonal antibodies (mabs) and their modified variants lacking effector function and dissected the mechanism by which some protect against antibody-enhanced lethal denv infection. we found that neutralizing modified mabs that recognize the fusion loop or the a strand epitopes on domains ii and iii of the envelope protein,respectively,act therapeutically by competing with and/or displacing enhancing antibodies. by analyzing these relationships,we developed a novel in vitro suppression-of-enhancement assay that predicts the ability of modified mabs to act therapeutically against antibody-enhanced disease in vivo. these studies provide new insight into the biology of denv pathogenesis and the requirements for antibodies to treat lethal denv disease. © 2013 williams et al.