Role of NS1 antibodies in the pathogenesis of acute dengue infection

Abstract

The role of NS1-specific antibodies in the pathogenesis of dengue virus infection is of particular interest to the dengue field, yet remains poorly understood. We therefore investigated the immunoglobulin responses of patients with dengue fever (DF) and dengue hemorrhagic fever (DHF) to NS1. Antibody responses to recombinant-NS1 were assessed in serum samples obtained throughout illness of patients with acute secondary DENV1 and DENV2 infection by ELISA. NS1 antibody titres were significantly higher in patients with DHF compared to those with DF for both serotypes, during the critical phase of illness. Antibody responses were further assessed to NS1 peptides and showed that in both acute secondary DENV1 and DENV2 infection, the antibody repertoire of DF and DHF patients is directed towards distinct regions of the NS1 protein. Further experiments in healthy individuals, with either past severe dengue or past asymptomatic dengue infection revealed that individuals with past inapparent disease mounted antibody responses directed to the same NS1 epitope regions as those with mild acute infection (DF). Our results suggest that the specific epitope target of NS1-antibodies generated by patients could predict disease severity and be of potential therapeutic benefit in aiding vaccine and treatment design.