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Identification of Continuous Human B-Cell Epitopes in the Envelope Glycoprotein of Dengue Virus Type 3 (DENV-3)

BACKGROUND: Dengue virus infection is a growing global public health concern in tropical and subtropical regions of the world. Dengue vaccine development has been hampered by concerns that cross-reactive immunological memory elicited by a candidate vaccine could increase the risk of development of m...

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Autores principales: da Silva, Andréa N. M. Rangel, Nascimento, Eduardo J. M., Cordeiro, Marli Tenório, Gil, Laura H. V. G., Abath, Frederico G. C., Montenegro, Silvia M. L., Marques, Ernesto T. A.
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2760205/
https://www.ncbi.nlm.nih.gov/pubmed/19826631
http://dx.doi.org/10.1371/journal.pone.0007425
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author da Silva, Andréa N. M. Rangel
Nascimento, Eduardo J. M.
Cordeiro, Marli Tenório
Gil, Laura H. V. G.
Abath, Frederico G. C.
Montenegro, Silvia M. L.
Marques, Ernesto T. A.
author_facet da Silva, Andréa N. M. Rangel
Nascimento, Eduardo J. M.
Cordeiro, Marli Tenório
Gil, Laura H. V. G.
Abath, Frederico G. C.
Montenegro, Silvia M. L.
Marques, Ernesto T. A.
author_sort da Silva, Andréa N. M. Rangel
collection PubMed
description BACKGROUND: Dengue virus infection is a growing global public health concern in tropical and subtropical regions of the world. Dengue vaccine development has been hampered by concerns that cross-reactive immunological memory elicited by a candidate vaccine could increase the risk of development of more severe clinical forms. One possible strategy to reduce risks associated with a dengue vaccine is the development of a vaccine composed of selected critical epitopes of each of the serotypes. METHODOLOGY/PRINCIPAL FINDINGS: Synthetic peptides were used to identify B-cell epitopes in the envelope (E) glycoprotein of dengue virus type 3 (DENV-3). Eleven linear, immunodominant epitopes distributed in five regions at amino acid (aa) positions: 51–65, 71–90, 131–170, 196–210 and 246–260 were identified by employing an enzyme- linked immunosorbent assay (ELISA), using a pool of human sera from dengue type 3 infected individuals. Peptides 11 (aa51–65), 27 and 28 (aa131–150) also reacted with dengue 1 (DENV-1) and dengue 2 (DENV-2) patient sera as analyzed through the ROC curves generated for each peptide by ELISA and might have serotype specific diagnostic potential. Mice immunized against each one of the five immunogenic regions showed epitopes 51–65, 131–170, 196–210 and 246–260 elicited the highest antibody response and epitopes131–170, 196–210 and 246–260, elicited IFN-γ production and T CD4+ cell response, as evaluated by ELISA and ELISPOT assays respectively. CONCLUSIONS/SIGNIFICANCE: Our study identified several useful immunodominant IgG-specific epitopes on the envelope of DENV-3. They are important tools for understanding the mechanisms involved in antibody dependent enhancement and immunity. If proven protective and safe, in conjunction with others well-documented epitopes, they might be included into a candidate epitope-based vaccine.
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spelling pubmed-27602052009-10-14 Identification of Continuous Human B-Cell Epitopes in the Envelope Glycoprotein of Dengue Virus Type 3 (DENV-3) da Silva, Andréa N. M. Rangel Nascimento, Eduardo J. M. Cordeiro, Marli Tenório Gil, Laura H. V. G. Abath, Frederico G. C. Montenegro, Silvia M. L. Marques, Ernesto T. A. PLoS One Research Article BACKGROUND: Dengue virus infection is a growing global public health concern in tropical and subtropical regions of the world. Dengue vaccine development has been hampered by concerns that cross-reactive immunological memory elicited by a candidate vaccine could increase the risk of development of more severe clinical forms. One possible strategy to reduce risks associated with a dengue vaccine is the development of a vaccine composed of selected critical epitopes of each of the serotypes. METHODOLOGY/PRINCIPAL FINDINGS: Synthetic peptides were used to identify B-cell epitopes in the envelope (E) glycoprotein of dengue virus type 3 (DENV-3). Eleven linear, immunodominant epitopes distributed in five regions at amino acid (aa) positions: 51–65, 71–90, 131–170, 196–210 and 246–260 were identified by employing an enzyme- linked immunosorbent assay (ELISA), using a pool of human sera from dengue type 3 infected individuals. Peptides 11 (aa51–65), 27 and 28 (aa131–150) also reacted with dengue 1 (DENV-1) and dengue 2 (DENV-2) patient sera as analyzed through the ROC curves generated for each peptide by ELISA and might have serotype specific diagnostic potential. Mice immunized against each one of the five immunogenic regions showed epitopes 51–65, 131–170, 196–210 and 246–260 elicited the highest antibody response and epitopes131–170, 196–210 and 246–260, elicited IFN-γ production and T CD4+ cell response, as evaluated by ELISA and ELISPOT assays respectively. CONCLUSIONS/SIGNIFICANCE: Our study identified several useful immunodominant IgG-specific epitopes on the envelope of DENV-3. They are important tools for understanding the mechanisms involved in antibody dependent enhancement and immunity. If proven protective and safe, in conjunction with others well-documented epitopes, they might be included into a candidate epitope-based vaccine. Public Library of Science 2009-10-13 /pmc/articles/PMC2760205/ /pubmed/19826631 http://dx.doi.org/10.1371/journal.pone.0007425 Text en Rangel da Silva et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
da Silva, Andréa N. M. Rangel
Nascimento, Eduardo J. M.
Cordeiro, Marli Tenório
Gil, Laura H. V. G.
Abath, Frederico G. C.
Montenegro, Silvia M. L.
Marques, Ernesto T. A.
Identification of Continuous Human B-Cell Epitopes in the Envelope Glycoprotein of Dengue Virus Type 3 (DENV-3)
title Identification of Continuous Human B-Cell Epitopes in the Envelope Glycoprotein of Dengue Virus Type 3 (DENV-3)
title_full Identification of Continuous Human B-Cell Epitopes in the Envelope Glycoprotein of Dengue Virus Type 3 (DENV-3)
title_fullStr Identification of Continuous Human B-Cell Epitopes in the Envelope Glycoprotein of Dengue Virus Type 3 (DENV-3)
title_full_unstemmed Identification of Continuous Human B-Cell Epitopes in the Envelope Glycoprotein of Dengue Virus Type 3 (DENV-3)
title_short Identification of Continuous Human B-Cell Epitopes in the Envelope Glycoprotein of Dengue Virus Type 3 (DENV-3)
title_sort identification of continuous human b-cell epitopes in the envelope glycoprotein of dengue virus type 3 (denv-3)
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2760205/
https://www.ncbi.nlm.nih.gov/pubmed/19826631
http://dx.doi.org/10.1371/journal.pone.0007425
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