Characterization of Human Anti-Dengue NS1 Monoclonal Antibodies Derived from Patients Infected with DENV-2

Abstract

Mouse antibodies specific to dengue NS1 have been widely studied for their cross-reactivity with several human molecules. This is the first cross-reactivity study of dengue NS1 specific human monoclonal antibodies (HuMAbs), isolated from DENV2 infected patients. Nine anti-NS1 HuMAbs derived mainly from convalescent-phase patients with secondary DENV-2 infections were characterized. Their cross-reactivity with plasminogen, thrombin, and endothelial cells was investigated, and then plasmin-formation assays were performed. All anti-NS1 HuMAbs were cross-reactive with human plasminogen (Plg), but not thrombin and endothelial cells. Moreover, all HuMAbs that showed cross-reactivity with Plg converted Plg to plasmin in a plasmin-formation assay. These results suggest the implications and drawbacks of anti-NS1 antibodies for immunotherapy.