Role of NS1 antibodies in the pathogenesis of acute secondary dengue infection

Deshni Jayathilaka,Pathum Asela Perera,Dhanushka Herath,Geethal S Bandara Jayarathna,Laksiri Gomes,Ananda Wijewickrama,Clare S Hardman,Gathsaurie Neelika Malavige,Chandima Jeewandara,Graham S Ogg,Samitha Fernando

doi:10.1038/s41467-018-07667-z

Deshni Jayathilaka, Pathum Asela Perera + Show 9 more

Open Access

https://doi.org/10.1038/s41467-018-07667-z

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Abstract

The role of NS1-specific antibodies in the pathogenesis of dengue virus infection is poorly understood. Here we investigate the immunoglobulin responses of patients with dengue fever (DF) and dengue hemorrhagic fever (DHF) to NS1. Antibody responses to recombinant-NS1 are assessed in serum samples throughout illness of patients with acute secondary DENV1 and DENV2 infection by ELISA. NS1 antibody titres are significantly higher in patients with DHF compared to those with DF for both serotypes, during the critical phase of illness. Furthermore, during both acute secondary DENV1 and DENV2 infection, the antibody repertoire of DF and DHF patients is directed towards distinct regions of the NS1 protein. In addition, healthy individuals, with past non-severe dengue infection have a similar antibody repertoire as those with mild acute infection (DF). Therefore, antibodies that target specific NS1 epitopes could predict disease severity and be of potential benefit in aiding vaccine and treatment design.

Highlights

The role of non-structural protein 1 (NS1)-specific antibodies in the pathogenesis of dengue virus infection is poorly understood
The NS1 antibody levels were assessed by an in-house enzyme-linked immunosorbent assay (ELISA), in Dengue virus (DENV)-seronegative individuals (n = 20), in those who were seropositive for DENV but had never been hospitalized for a febrile infection and were considered to have past nonsevere dengue (NSD) (n = 36) and those who had a past history of dengue hemorrhagic fever (DHF) and were considered to have past severe dengue (SD) (n = 34)
We found that NS1 antibody levels were significantly higher in healthy individuals who had past SD when compared with those who had past non-severe dengue (NSD)

Summary

Introduction

The role of NS1-specific antibodies in the pathogenesis of dengue virus infection is poorly understood. In contrast to the data in the above studies, some investigations in dengue mouse models have shown that mice injected with sera from dengue-infected mice or monoclonal antibodies to NS1, have significantly reduced vascular leak, implying a protective role for antibodies to NS115. It is currently not clear if antibodies targeted to specific regions of dengue NS1 protein may play differential roles in the protection or pathogenesis of dengue fever in humans. There are limited data on the target, isotype and function of anti-NS1 antibodies in acute secondary dengue infections, which account for most cases of severe dengue infection

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