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Comprehensive mapping infection-enhancing epitopes of dengue pr protein using polyclonal antibody against prM

Dengue vaccine development is considered a global public health priority, but the antibody-dependent enhancement (ADE) issues have critically restricted vaccine development. Recent findings have demonstrated that pre-membrane (prM) protein was involved in dengue virus (DENV) infection enhancement. A...

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Autores principales: Luo, Yayan, Guo, Xiaolan, Yan, Huijun, Fang, Danyun, Zeng, Gucheng, Zhou, Junmei, Jiang, Lifang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4480844/
https://www.ncbi.nlm.nih.gov/pubmed/25822571
http://dx.doi.org/10.1007/s00253-015-6538-9
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author Luo, Yayan
Guo, Xiaolan
Yan, Huijun
Fang, Danyun
Zeng, Gucheng
Zhou, Junmei
Jiang, Lifang
author_facet Luo, Yayan
Guo, Xiaolan
Yan, Huijun
Fang, Danyun
Zeng, Gucheng
Zhou, Junmei
Jiang, Lifang
author_sort Luo, Yayan
collection PubMed
description Dengue vaccine development is considered a global public health priority, but the antibody-dependent enhancement (ADE) issues have critically restricted vaccine development. Recent findings have demonstrated that pre-membrane (prM) protein was involved in dengue virus (DENV) infection enhancement. Although the importance of prM antibodies have been well characterized, only a few epitopes in DENV prM protein have ever been identified. In this study, we screened five potential linear epitopes located at positions pr1 (1-16aa), pr3 (13-28aa), pr4 (19-34aa), pr9 (49-64aa), and pr10 (55-70aa) in pr protein using peptide scanning and comprehensive bioinformatics analysis. Then, we found that only pr4 (19-34aa) could elicit high-titer antibodies in Balb/c mice, and this epitope could react with sera from DENV2-infected patients, suggesting that specific antibodies against epitope peptide pr4 were elicited in both DENV-infected mice and human. In addition, our data demonstrated that anti-pr4 sera showed limited neutralizing activity but significant ADE activity toward standard DENV serotypes and imDENV. Hence, it seems responsible to hypothesize that anti-pr4 serum was infection-enhancing antibody and pr4 was infection-enhancing epitope. In conclusion, we characterized a novel infection-enhancing epitope on dengue pr protein, a finding that may provide new insight into the pathogenesis of DENV infection and contribute to dengue vaccine design.
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spelling pubmed-44808442015-07-02 Comprehensive mapping infection-enhancing epitopes of dengue pr protein using polyclonal antibody against prM Luo, Yayan Guo, Xiaolan Yan, Huijun Fang, Danyun Zeng, Gucheng Zhou, Junmei Jiang, Lifang Appl Microbiol Biotechnol Applied Genetics and Molecular Biotechnology Dengue vaccine development is considered a global public health priority, but the antibody-dependent enhancement (ADE) issues have critically restricted vaccine development. Recent findings have demonstrated that pre-membrane (prM) protein was involved in dengue virus (DENV) infection enhancement. Although the importance of prM antibodies have been well characterized, only a few epitopes in DENV prM protein have ever been identified. In this study, we screened five potential linear epitopes located at positions pr1 (1-16aa), pr3 (13-28aa), pr4 (19-34aa), pr9 (49-64aa), and pr10 (55-70aa) in pr protein using peptide scanning and comprehensive bioinformatics analysis. Then, we found that only pr4 (19-34aa) could elicit high-titer antibodies in Balb/c mice, and this epitope could react with sera from DENV2-infected patients, suggesting that specific antibodies against epitope peptide pr4 were elicited in both DENV-infected mice and human. In addition, our data demonstrated that anti-pr4 sera showed limited neutralizing activity but significant ADE activity toward standard DENV serotypes and imDENV. Hence, it seems responsible to hypothesize that anti-pr4 serum was infection-enhancing antibody and pr4 was infection-enhancing epitope. In conclusion, we characterized a novel infection-enhancing epitope on dengue pr protein, a finding that may provide new insight into the pathogenesis of DENV infection and contribute to dengue vaccine design. Springer Berlin Heidelberg 2015-03-31 2015 /pmc/articles/PMC4480844/ /pubmed/25822571 http://dx.doi.org/10.1007/s00253-015-6538-9 Text en © The Author(s) 2015 https://creativecommons.org/licenses/by/4.0/ Open Access This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.
spellingShingle Applied Genetics and Molecular Biotechnology
Luo, Yayan
Guo, Xiaolan
Yan, Huijun
Fang, Danyun
Zeng, Gucheng
Zhou, Junmei
Jiang, Lifang
Comprehensive mapping infection-enhancing epitopes of dengue pr protein using polyclonal antibody against prM
title Comprehensive mapping infection-enhancing epitopes of dengue pr protein using polyclonal antibody against prM
title_full Comprehensive mapping infection-enhancing epitopes of dengue pr protein using polyclonal antibody against prM
title_fullStr Comprehensive mapping infection-enhancing epitopes of dengue pr protein using polyclonal antibody against prM
title_full_unstemmed Comprehensive mapping infection-enhancing epitopes of dengue pr protein using polyclonal antibody against prM
title_short Comprehensive mapping infection-enhancing epitopes of dengue pr protein using polyclonal antibody against prM
title_sort comprehensive mapping infection-enhancing epitopes of dengue pr protein using polyclonal antibody against prm
topic Applied Genetics and Molecular Biotechnology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4480844/
https://www.ncbi.nlm.nih.gov/pubmed/25822571
http://dx.doi.org/10.1007/s00253-015-6538-9
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