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In silico design of a Zika virus non-structural protein 5 aiming vaccine protection against zika and dengue in different human populations

BACKGROUND: The arboviruses Zika virus (ZIKV) and Dengue virus (DENV) have important epidemiological impact in Brazil and other tropical regions of the world. Recently, it was shown that previous humoral immunity to DENV enhances ZIKV replication in vitro, which may lead to more severe forms of the...

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Autores principales: dos Santos Franco, Lorrany, Oliveira Vidal, Paloma, Amorim, Jaime Henrique
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5701345/
https://www.ncbi.nlm.nih.gov/pubmed/29169357
http://dx.doi.org/10.1186/s12929-017-0395-z
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author dos Santos Franco, Lorrany
Oliveira Vidal, Paloma
Amorim, Jaime Henrique
author_facet dos Santos Franco, Lorrany
Oliveira Vidal, Paloma
Amorim, Jaime Henrique
author_sort dos Santos Franco, Lorrany
collection PubMed
description BACKGROUND: The arboviruses Zika virus (ZIKV) and Dengue virus (DENV) have important epidemiological impact in Brazil and other tropical regions of the world. Recently, it was shown that previous humoral immunity to DENV enhances ZIKV replication in vitro, which may lead to more severe forms of the disease. Thus, traditional approaches of vaccine development aiming to control viral infection through neutralizing antibodies may induce cross-reactive enhancing antibodies. In contrast, cellular immune response was shown to be capable of controlling DENV infection independently of antibodies. The aim of the present study was to design a flavivirus NS5 protein capable of inducing a cellular immune response against DENV and ZIKV. METHODS: A consensus sequence of ZIKV NS5 protein was designed among isolates from various continents. Epitopes were predicted for the most prevalent alleles of class I and II HLA in the Brazilian population. Then, this epitopes were analyzed with regard to their conservation, population coverage and distribution along the whole antigen. RESULTS: Nineteen epitopes predicted to be more reactive (percentile rank <1) and 100% conserved among ZIKV and DENV serotypes were selected. The distribution of such epitopes along the protein was shown on a three-dimensional model and population coverage was calculated for different regions of the world. The designed protein was predicted to be stable and the distribution of selected epitopes was shown to be homogeneous along domains. The population coverage of selected epitopes was higher than 50% for most of tropical areas of the world. CONCLUSION: Such results indicate that the proposed antigen has the potential to induce protective cellular immune response to ZIKV and DENV in different human populations of the world. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12929-017-0395-z) contains supplementary material, which is available to authorized users.
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spelling pubmed-57013452017-12-01 In silico design of a Zika virus non-structural protein 5 aiming vaccine protection against zika and dengue in different human populations dos Santos Franco, Lorrany Oliveira Vidal, Paloma Amorim, Jaime Henrique J Biomed Sci Research BACKGROUND: The arboviruses Zika virus (ZIKV) and Dengue virus (DENV) have important epidemiological impact in Brazil and other tropical regions of the world. Recently, it was shown that previous humoral immunity to DENV enhances ZIKV replication in vitro, which may lead to more severe forms of the disease. Thus, traditional approaches of vaccine development aiming to control viral infection through neutralizing antibodies may induce cross-reactive enhancing antibodies. In contrast, cellular immune response was shown to be capable of controlling DENV infection independently of antibodies. The aim of the present study was to design a flavivirus NS5 protein capable of inducing a cellular immune response against DENV and ZIKV. METHODS: A consensus sequence of ZIKV NS5 protein was designed among isolates from various continents. Epitopes were predicted for the most prevalent alleles of class I and II HLA in the Brazilian population. Then, this epitopes were analyzed with regard to their conservation, population coverage and distribution along the whole antigen. RESULTS: Nineteen epitopes predicted to be more reactive (percentile rank <1) and 100% conserved among ZIKV and DENV serotypes were selected. The distribution of such epitopes along the protein was shown on a three-dimensional model and population coverage was calculated for different regions of the world. The designed protein was predicted to be stable and the distribution of selected epitopes was shown to be homogeneous along domains. The population coverage of selected epitopes was higher than 50% for most of tropical areas of the world. CONCLUSION: Such results indicate that the proposed antigen has the potential to induce protective cellular immune response to ZIKV and DENV in different human populations of the world. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12929-017-0395-z) contains supplementary material, which is available to authorized users. BioMed Central 2017-11-23 /pmc/articles/PMC5701345/ /pubmed/29169357 http://dx.doi.org/10.1186/s12929-017-0395-z Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
dos Santos Franco, Lorrany
Oliveira Vidal, Paloma
Amorim, Jaime Henrique
In silico design of a Zika virus non-structural protein 5 aiming vaccine protection against zika and dengue in different human populations
title In silico design of a Zika virus non-structural protein 5 aiming vaccine protection against zika and dengue in different human populations
title_full In silico design of a Zika virus non-structural protein 5 aiming vaccine protection against zika and dengue in different human populations
title_fullStr In silico design of a Zika virus non-structural protein 5 aiming vaccine protection against zika and dengue in different human populations
title_full_unstemmed In silico design of a Zika virus non-structural protein 5 aiming vaccine protection against zika and dengue in different human populations
title_short In silico design of a Zika virus non-structural protein 5 aiming vaccine protection against zika and dengue in different human populations
title_sort in silico design of a zika virus non-structural protein 5 aiming vaccine protection against zika and dengue in different human populations
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5701345/
https://www.ncbi.nlm.nih.gov/pubmed/29169357
http://dx.doi.org/10.1186/s12929-017-0395-z
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