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...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Adewale Oluwaseun Fadaka, Nicole Remaliah Samantha Sibuyi, Darius Riziki Martin, Mediline Goboza, Ashwil Klein, Abram Madimabe Madiehe, Mervin Meyer
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6f4f870cfe6c482bb32b00dc9e03c91e
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:6f4f870cfe6c482bb32b00dc9e03c91e
record_format	dspace
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
work_keys_str_mv	AT adewaleoluwaseunfadaka immunoinformaticsdesignofanovelepitopebasedvaccinecandidateagainstdenguevirus AT nicoleremaliahsamanthasibuyi immunoinformaticsdesignofanovelepitopebasedvaccinecandidateagainstdenguevirus AT dariusrizikimartin immunoinformaticsdesignofanovelepitopebasedvaccinecandidateagainstdenguevirus AT medilinegoboza immunoinformaticsdesignofanovelepitopebasedvaccinecandidateagainstdenguevirus AT ashwilklein immunoinformaticsdesignofanovelepitopebasedvaccinecandidateagainstdenguevirus AT abrammadimabemadiehe immunoinformaticsdesignofanovelepitopebasedvaccinecandidateagainstdenguevirus AT mervinmeyer immunoinformaticsdesignofanovelepitopebasedvaccinecandidateagainstdenguevirus
_version_	1718377803757387776

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

Ejemplares similares