Immunoinformatics design of a novel epitope-based vaccine candidate against dengue virus

Abstract Dengue poses a global health threat, which will persist without therapeutic intervention. Immunity induced by exposure to one serotype does not confer long-term protection against secondary infection with other serotypes and is potentially capable of enhancing this infection. Although vacci...

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Autores principales: Adewale Oluwaseun Fadaka, Nicole Remaliah Samantha Sibuyi, Darius Riziki Martin, Mediline Goboza, Ashwil Klein, Abram Madimabe Madiehe, Mervin Meyer
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Publicado: Nature Portfolio 2021
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spelling oai:doaj.org-article:6f4f870cfe6c482bb32b00dc9e03c91e2021-12-02T18:37:08ZImmunoinformatics design of a novel epitope-based vaccine candidate against dengue virus10.1038/s41598-021-99227-72045-2322https://doaj.org/article/6f4f870cfe6c482bb32b00dc9e03c91e2021-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-99227-7https://doaj.org/toc/2045-2322Abstract Dengue poses a global health threat, which will persist without therapeutic intervention. Immunity induced by exposure to one serotype does not confer long-term protection against secondary infection with other serotypes and is potentially capable of enhancing this infection. Although vaccination is believed to induce durable and protective responses against all the dengue virus (DENV) serotypes in order to reduce the burden posed by this virus, the development of a safe and efficacious vaccine remains a challenge. Immunoinformatics and computational vaccinology have been utilized in studies of infectious diseases to provide insight into the host–pathogen interactions thus justifying their use in vaccine development. Since vaccination is the best bet to reduce the burden posed by DENV, this study is aimed at developing a multi-epitope based vaccines for dengue control. Combined approaches of reverse vaccinology and immunoinformatics were utilized to design multi-epitope based vaccine from the sequence of DENV. Specifically, BCPreds and IEDB servers were used to predict the B-cell and T-cell epitopes, respectively. Molecular docking was carried out using Schrödinger, PATCHDOCK and FIREDOCK. Codon optimization and in silico cloning were done using JCAT and SnapGene respectively. Finally, the efficiency and stability of the designed vaccines were assessed by an in silico immune simulation and molecular dynamic simulation, respectively. The predicted epitopes were prioritized using in-house criteria. Four candidate vaccines (DV-1–4) were designed using suitable adjuvant and linkers in addition to the shortlisted epitopes. The binding interactions of these vaccines against the receptors TLR-2, TLR-4, MHC-1 and MHC-2 show that these candidate vaccines perfectly fit into the binding domains of the receptors. In addition, DV-1 has a better binding energies of − 60.07, − 63.40, − 69.89 kcal/mol against MHC-1, TLR-2, and TLR-4, with respect to the other vaccines. All the designed vaccines were highly antigenic, soluble, non-allergenic, non-toxic, flexible, and topologically assessable. The immune simulation analysis showed that DV-1 may elicit specific immune response against dengue virus. Moreover, codon optimization and in silico cloning validated the expressions of all the designed vaccines in E. coli. Finally, the molecular dynamic study shows that DV-1 is stable with minimum RMSF against TLR4. Immunoinformatics tools are now applied to screen genomes of interest for possible vaccine target. The designed vaccine candidates may be further experimentally investigated as potential vaccines capable of providing definitive preventive measure against dengue virus infection.Adewale Oluwaseun FadakaNicole Remaliah Samantha SibuyiDarius Riziki MartinMediline GobozaAshwil KleinAbram Madimabe MadieheMervin MeyerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-22 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Adewale Oluwaseun Fadaka
Nicole Remaliah Samantha Sibuyi
Darius Riziki Martin
Mediline Goboza
Ashwil Klein
Abram Madimabe Madiehe
Mervin Meyer
Immunoinformatics design of a novel epitope-based vaccine candidate against dengue virus
description Abstract Dengue poses a global health threat, which will persist without therapeutic intervention. Immunity induced by exposure to one serotype does not confer long-term protection against secondary infection with other serotypes and is potentially capable of enhancing this infection. Although vaccination is believed to induce durable and protective responses against all the dengue virus (DENV) serotypes in order to reduce the burden posed by this virus, the development of a safe and efficacious vaccine remains a challenge. Immunoinformatics and computational vaccinology have been utilized in studies of infectious diseases to provide insight into the host–pathogen interactions thus justifying their use in vaccine development. Since vaccination is the best bet to reduce the burden posed by DENV, this study is aimed at developing a multi-epitope based vaccines for dengue control. Combined approaches of reverse vaccinology and immunoinformatics were utilized to design multi-epitope based vaccine from the sequence of DENV. Specifically, BCPreds and IEDB servers were used to predict the B-cell and T-cell epitopes, respectively. Molecular docking was carried out using Schrödinger, PATCHDOCK and FIREDOCK. Codon optimization and in silico cloning were done using JCAT and SnapGene respectively. Finally, the efficiency and stability of the designed vaccines were assessed by an in silico immune simulation and molecular dynamic simulation, respectively. The predicted epitopes were prioritized using in-house criteria. Four candidate vaccines (DV-1–4) were designed using suitable adjuvant and linkers in addition to the shortlisted epitopes. The binding interactions of these vaccines against the receptors TLR-2, TLR-4, MHC-1 and MHC-2 show that these candidate vaccines perfectly fit into the binding domains of the receptors. In addition, DV-1 has a better binding energies of − 60.07, − 63.40, − 69.89 kcal/mol against MHC-1, TLR-2, and TLR-4, with respect to the other vaccines. All the designed vaccines were highly antigenic, soluble, non-allergenic, non-toxic, flexible, and topologically assessable. The immune simulation analysis showed that DV-1 may elicit specific immune response against dengue virus. Moreover, codon optimization and in silico cloning validated the expressions of all the designed vaccines in E. coli. Finally, the molecular dynamic study shows that DV-1 is stable with minimum RMSF against TLR4. Immunoinformatics tools are now applied to screen genomes of interest for possible vaccine target. The designed vaccine candidates may be further experimentally investigated as potential vaccines capable of providing definitive preventive measure against dengue virus infection.
format article
author Adewale Oluwaseun Fadaka
Nicole Remaliah Samantha Sibuyi
Darius Riziki Martin
Mediline Goboza
Ashwil Klein
Abram Madimabe Madiehe
Mervin Meyer
author_facet Adewale Oluwaseun Fadaka
Nicole Remaliah Samantha Sibuyi
Darius Riziki Martin
Mediline Goboza
Ashwil Klein
Abram Madimabe Madiehe
Mervin Meyer
author_sort Adewale Oluwaseun Fadaka
title Immunoinformatics design of a novel epitope-based vaccine candidate against dengue virus
title_short Immunoinformatics design of a novel epitope-based vaccine candidate against dengue virus
title_full Immunoinformatics design of a novel epitope-based vaccine candidate against dengue virus
title_fullStr Immunoinformatics design of a novel epitope-based vaccine candidate against dengue virus
title_full_unstemmed Immunoinformatics design of a novel epitope-based vaccine candidate against dengue virus
title_sort immunoinformatics design of a novel epitope-based vaccine candidate against dengue virus
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/6f4f870cfe6c482bb32b00dc9e03c91e
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