An Epitope-Substituted DNA Vaccine Improves Safety and Immunogenicity against Dengue Virus Type 2.
Dengue virus (DENV), a global disease, is divided into four serotypes (DENV1-4). Cross-reactive and non-neutralizing antibodies against envelope (E) protein of DENV bind to the Fcγ receptors (FcγR) of cells, and thereby exacerbate viral infection by heterologous serotypes via antibody-dependent enha...
Published in: | PLOS Neglected Tropical Diseases |
---|---|
Main Authors: | , , , , , , |
Format: | Article in Journal/Newspaper |
Language: | English |
Published: |
Public Library of Science (PLoS)
2015
|
Subjects: | |
Online Access: | https://doi.org/10.1371/journal.pntd.0003903 https://doaj.org/article/4a7a10e8c138468ba810de9e1756d405 |
id |
ftdoajarticles:oai:doaj.org/article:4a7a10e8c138468ba810de9e1756d405 |
---|---|
record_format |
openpolar |
spelling |
ftdoajarticles:oai:doaj.org/article:4a7a10e8c138468ba810de9e1756d405 2023-05-15T15:11:28+02:00 An Epitope-Substituted DNA Vaccine Improves Safety and Immunogenicity against Dengue Virus Type 2. Chung-Tao Tang Pi-Chun Li I-Ju Liu Mei-Ying Liao Chiung-Yi Chiu Day-Yu Chao Han-Chung Wu 2015-01-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0003903 https://doaj.org/article/4a7a10e8c138468ba810de9e1756d405 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC4489899?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0003903 https://doaj.org/article/4a7a10e8c138468ba810de9e1756d405 PLoS Neglected Tropical Diseases, Vol 9, Iss 7, p e0003903 (2015) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2015 ftdoajarticles https://doi.org/10.1371/journal.pntd.0003903 2022-12-31T16:33:41Z Dengue virus (DENV), a global disease, is divided into four serotypes (DENV1-4). Cross-reactive and non-neutralizing antibodies against envelope (E) protein of DENV bind to the Fcγ receptors (FcγR) of cells, and thereby exacerbate viral infection by heterologous serotypes via antibody-dependent enhancement (ADE). Identification and modification of enhancing epitopes may mitigate enhancement of DENV infection. In this study, we characterized the cross-reactive DB21-6 and DB39-2 monoclonal antibodies (mAbs) against domain I-II of DENV; these antibodies poorly neutralized and potently enhanced DENV infection both in vitro and in vivo. In addition, two enhancing mAbs, DB21-6 and DB39-2, were observed to compete with sera antibodies from patients infected with dengue. The epitopes of these enhancing mAbs were identified using phage display, structural prediction, and mapping of virus-like particle (VLP) mutants. N8, R9, V12, and E13 are the reactive residues of DB21-6, while N8, R9, and E13 are the reactive residues of DB39-2. N8 substitution tends to maintain VLP secretion, and decreases the binding activity of DB21-6 and DB39-2. The immunized sera from N8 substitution (N8R) DNA vaccine exerted greater neutralizing and protective activity than wild-type (WT)-immunized sera, both in vitro and in vivo. Furthermore, treatment with N8R-immunized sera reduced the enhancement of mortality in AG129 mice. These results support identification and substitution of enhancing epitope as a novel strategy for developing safe dengue vaccines. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 9 7 e0003903 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Chung-Tao Tang Pi-Chun Li I-Ju Liu Mei-Ying Liao Chiung-Yi Chiu Day-Yu Chao Han-Chung Wu An Epitope-Substituted DNA Vaccine Improves Safety and Immunogenicity against Dengue Virus Type 2. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Dengue virus (DENV), a global disease, is divided into four serotypes (DENV1-4). Cross-reactive and non-neutralizing antibodies against envelope (E) protein of DENV bind to the Fcγ receptors (FcγR) of cells, and thereby exacerbate viral infection by heterologous serotypes via antibody-dependent enhancement (ADE). Identification and modification of enhancing epitopes may mitigate enhancement of DENV infection. In this study, we characterized the cross-reactive DB21-6 and DB39-2 monoclonal antibodies (mAbs) against domain I-II of DENV; these antibodies poorly neutralized and potently enhanced DENV infection both in vitro and in vivo. In addition, two enhancing mAbs, DB21-6 and DB39-2, were observed to compete with sera antibodies from patients infected with dengue. The epitopes of these enhancing mAbs were identified using phage display, structural prediction, and mapping of virus-like particle (VLP) mutants. N8, R9, V12, and E13 are the reactive residues of DB21-6, while N8, R9, and E13 are the reactive residues of DB39-2. N8 substitution tends to maintain VLP secretion, and decreases the binding activity of DB21-6 and DB39-2. The immunized sera from N8 substitution (N8R) DNA vaccine exerted greater neutralizing and protective activity than wild-type (WT)-immunized sera, both in vitro and in vivo. Furthermore, treatment with N8R-immunized sera reduced the enhancement of mortality in AG129 mice. These results support identification and substitution of enhancing epitope as a novel strategy for developing safe dengue vaccines. |
format |
Article in Journal/Newspaper |
author |
Chung-Tao Tang Pi-Chun Li I-Ju Liu Mei-Ying Liao Chiung-Yi Chiu Day-Yu Chao Han-Chung Wu |
author_facet |
Chung-Tao Tang Pi-Chun Li I-Ju Liu Mei-Ying Liao Chiung-Yi Chiu Day-Yu Chao Han-Chung Wu |
author_sort |
Chung-Tao Tang |
title |
An Epitope-Substituted DNA Vaccine Improves Safety and Immunogenicity against Dengue Virus Type 2. |
title_short |
An Epitope-Substituted DNA Vaccine Improves Safety and Immunogenicity against Dengue Virus Type 2. |
title_full |
An Epitope-Substituted DNA Vaccine Improves Safety and Immunogenicity against Dengue Virus Type 2. |
title_fullStr |
An Epitope-Substituted DNA Vaccine Improves Safety and Immunogenicity against Dengue Virus Type 2. |
title_full_unstemmed |
An Epitope-Substituted DNA Vaccine Improves Safety and Immunogenicity against Dengue Virus Type 2. |
title_sort |
epitope-substituted dna vaccine improves safety and immunogenicity against dengue virus type 2. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2015 |
url |
https://doi.org/10.1371/journal.pntd.0003903 https://doaj.org/article/4a7a10e8c138468ba810de9e1756d405 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 9, Iss 7, p e0003903 (2015) |
op_relation |
http://europepmc.org/articles/PMC4489899?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0003903 https://doaj.org/article/4a7a10e8c138468ba810de9e1756d405 |
op_doi |
https://doi.org/10.1371/journal.pntd.0003903 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
9 |
container_issue |
7 |
container_start_page |
e0003903 |
_version_ |
1766342314184146944 |