Antibodies Against Modified NS1 Wing Domain Peptide Protect Against Dengue Virus Infection

Abstract Dengue is the most common mosquito-transmitted viral infection for which an improved vaccine is still needed. Although nonstructural protein-1 (NS1) immunization can protect mice against dengue infection, molecular mimicry between NS1 and host proteins makes NS1-based vaccines challenging t...

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Main Authors: Yen-Chung Lai, Yung-Chun Chuang, Ching-Chuan Liu, Tzong-Shiann Ho, Yee-Shin Lin, Robert Anderson, Trai-Ming Yeh
Format: Article
Language:English
Published: Nature Publishing Group 2017-08-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-017-07308-3
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spelling doaj-99e85865988b468bbb37fefb11e3201a2020-12-08T00:33:11ZengNature Publishing GroupScientific Reports2045-23222017-08-017111510.1038/s41598-017-07308-3Antibodies Against Modified NS1 Wing Domain Peptide Protect Against Dengue Virus InfectionYen-Chung Lai0Yung-Chun Chuang1Ching-Chuan Liu2Tzong-Shiann Ho3Yee-Shin Lin4Robert Anderson5Trai-Ming Yeh6The Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung UniversityDepartment of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung UniversityDepartment of Pediatrics, College of Medicine, National Cheng Kung UniversityDepartment of Pediatrics, College of Medicine, National Cheng Kung UniversityDepartment of Microbiology and Immunology, College of Medicine, National Cheng Kung UniversityDepartments of Microbiology & Immunology and Pediatrics, and Canadian Center for Vaccinology, Dalhousie UniversityDepartment of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung UniversityAbstract Dengue is the most common mosquito-transmitted viral infection for which an improved vaccine is still needed. Although nonstructural protein-1 (NS1) immunization can protect mice against dengue infection, molecular mimicry between NS1 and host proteins makes NS1-based vaccines challenging to develop. Based on the epitope recognized by the anti-NS1 monoclonal Ab (mAb) 33D2 which recognizes a conserved NS1 wing domain (NS1-WD) region but not host proteins, we synthesized a modified NS1-WD peptide to immunize mice. We found that both mAb 33D2 and modified NS1-WD peptide immune sera could induce complement-dependent lysis of dengue-infected but not un-infected cells in vitro. Furthermore, either active immunization with the modified NS1-WD peptide or passive transfer of mAb 33D2 efficiently protected mice against all serotypes of dengue virus infection. More importantly, dengue patients with more antibodies recognized the modified NS1-WD peptide had less severe disease. Thus, the modified NS1-WD peptide is a promising dengue vaccine candidate.https://doi.org/10.1038/s41598-017-07308-3
collection DOAJ
language English
format Article
sources DOAJ
author Yen-Chung Lai
Yung-Chun Chuang
Ching-Chuan Liu
Tzong-Shiann Ho
Yee-Shin Lin
Robert Anderson
Trai-Ming Yeh
spellingShingle Yen-Chung Lai
Yung-Chun Chuang
Ching-Chuan Liu
Tzong-Shiann Ho
Yee-Shin Lin
Robert Anderson
Trai-Ming Yeh
Antibodies Against Modified NS1 Wing Domain Peptide Protect Against Dengue Virus Infection
Scientific Reports
author_facet Yen-Chung Lai
Yung-Chun Chuang
Ching-Chuan Liu
Tzong-Shiann Ho
Yee-Shin Lin
Robert Anderson
Trai-Ming Yeh
author_sort Yen-Chung Lai
title Antibodies Against Modified NS1 Wing Domain Peptide Protect Against Dengue Virus Infection
title_short Antibodies Against Modified NS1 Wing Domain Peptide Protect Against Dengue Virus Infection
title_full Antibodies Against Modified NS1 Wing Domain Peptide Protect Against Dengue Virus Infection
title_fullStr Antibodies Against Modified NS1 Wing Domain Peptide Protect Against Dengue Virus Infection
title_full_unstemmed Antibodies Against Modified NS1 Wing Domain Peptide Protect Against Dengue Virus Infection
title_sort antibodies against modified ns1 wing domain peptide protect against dengue virus infection
publisher Nature Publishing Group
series Scientific Reports
issn 2045-2322
publishDate 2017-08-01
description Abstract Dengue is the most common mosquito-transmitted viral infection for which an improved vaccine is still needed. Although nonstructural protein-1 (NS1) immunization can protect mice against dengue infection, molecular mimicry between NS1 and host proteins makes NS1-based vaccines challenging to develop. Based on the epitope recognized by the anti-NS1 monoclonal Ab (mAb) 33D2 which recognizes a conserved NS1 wing domain (NS1-WD) region but not host proteins, we synthesized a modified NS1-WD peptide to immunize mice. We found that both mAb 33D2 and modified NS1-WD peptide immune sera could induce complement-dependent lysis of dengue-infected but not un-infected cells in vitro. Furthermore, either active immunization with the modified NS1-WD peptide or passive transfer of mAb 33D2 efficiently protected mice against all serotypes of dengue virus infection. More importantly, dengue patients with more antibodies recognized the modified NS1-WD peptide had less severe disease. Thus, the modified NS1-WD peptide is a promising dengue vaccine candidate.
url https://doi.org/10.1038/s41598-017-07308-3
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