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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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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