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Protective Role of NS1-Specific Antibodies in the Immune Response to Dengue Virus through Antibody-Dependent Cellular Cytotoxicity.

Accepted version
Peer-reviewed

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Authors

Sanchez-Vargas, Luis A  ORCID logo  https://orcid.org/0000-0003-4622-5427
Sousa, David 
Casale, Nicole A 

Abstract

BACKGROUND: Dengue virus (DENV) non-structural protein 1 (NS1) has multiple functions within infected cells, on the cell surface, and in secreted form, and is highly immunogenic. Immunity from previous DENV infections is known to exert both positive and negative effects on subsequent DENV infections, but the contribution of NS1-specific antibodies to these effects is incompletely understood. METHODS: We investigated the functions of NS1-specific antibodies and their significance in DENV infection. We analyzed plasma samples collected in a prospective cohort study prior to symptomatic or subclinical secondary DENV infection. We measured binding to purified recombinant NS1 protein and to NS1-expressing CEM cells, antibody-mediated NK cell activation by plate-bound NS1 protein, and antibody-dependent cellular cytotoxicity (ADCC) of NS1-expressing target cells. RESULTS: We found that antibody responses to NS1 were highly serotype-cross-reactive and that subjects who experienced subclinical DENV infection had significantly higher antibody responses to NS1 in pre-infection plasma than subjects who experienced symptomatic infection. We observed strong positive correlations between antibody binding and NK activation. CONCLUSIONS: These findings demonstrate the involvement of NS1-specific antibodies in ADCC and provide evidence for a protective effect of NS1-specific antibodies in secondary DENV infection.

Description

Keywords

NK cell activation, antibody-dependent cellular cytotoxicity (ADCC), dengue, non-structural protein 1 (NS1)

Journal Title

J Infect Dis

Conference Name

Journal ISSN

0022-1899
1537-6613

Volume Title

Publisher

Oxford University Press (OUP)
Sponsorship
National Institutes of Health (NIH) (via University of Rhode Island) (Subaward no. 0008048/12042022)