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Proteome-Wide and Protein-Specific Multi-Epitope Vaccine Constructs Against the Rift Valley Fever Virus Outbreak Using Integrated Omics Approaches

Rift Valley fever (RVF) is a viral disease caused by a member of the Bunyavirales family causing severe infections in humans. The RVF virus is an enveloped, negative-sense, single-stranded RNA virus that can infect both animals and humans. The symptoms associated with these infections span from mino...

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Autor principal: Albutti, Aqel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9195176/
https://www.ncbi.nlm.nih.gov/pubmed/35711778
http://dx.doi.org/10.3389/fmicb.2022.921683
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author Albutti, Aqel
author_facet Albutti, Aqel
author_sort Albutti, Aqel
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description Rift Valley fever (RVF) is a viral disease caused by a member of the Bunyavirales family causing severe infections in humans. The RVF virus is an enveloped, negative-sense, single-stranded RNA virus that can infect both animals and humans. The symptoms associated with these infections span from minor (fever and headaches) to severe (meningoencephalitis and hemorrhagic fever syndrome) symptoms. Despite the outbreaks of the RVF virus being reported in different parts of the world, no effective therapy is available. Herein, the development of an efficient vaccine is critical for the control of infections associated with the RVF virus. Moreover, computational vaccine approaches are helpful in the design of specific, safe, and stable peptide-based designs when compared to the conventional methods of vaccine development. In this study, the whole proteome of the virus, comprising four proteins (NP, L, GP, and NSP), was screened to find putative vaccine epitope sequences (T cell, B cell, and HTL) specific for each protein. These shortlisted epitopes were then combined with flexible linkers to design protein-specific and proteome-wide immunogenic multi-epitope-based vaccine constructs. The results revealed that these multi-epitope vaccine constructs (MEVCs) are strongly antigenic and non-allergenic in nature. The efficacy of these constructs was further validated by docking with immune receptors, which revealed strong binding interactions with human TLR8. Using the MD simulation approach, the binding stability and residual flexibility of the best vaccine construct (proteome-wide) were confirmed, which revealed stable dynamic and favorable features. Furthermore, in-silico cloning and immune simulation analysis confirmed the expression and production of immune factors, that is, IgM, IgG, and IL-6, against the proposed vaccine designs. Additionally, 3D models of all the MEVC constructs have been developed and evaluated for potential immunization against the RVF virus. Finally, the proteome-wide vaccine candidate (MEVC-PW-RVFV) with the highest immune reinforcement potential provides new insights into the development of future vaccines against the emerging RVF virus.
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spelling pubmed-91951762022-06-15 Proteome-Wide and Protein-Specific Multi-Epitope Vaccine Constructs Against the Rift Valley Fever Virus Outbreak Using Integrated Omics Approaches Albutti, Aqel Front Microbiol Microbiology Rift Valley fever (RVF) is a viral disease caused by a member of the Bunyavirales family causing severe infections in humans. The RVF virus is an enveloped, negative-sense, single-stranded RNA virus that can infect both animals and humans. The symptoms associated with these infections span from minor (fever and headaches) to severe (meningoencephalitis and hemorrhagic fever syndrome) symptoms. Despite the outbreaks of the RVF virus being reported in different parts of the world, no effective therapy is available. Herein, the development of an efficient vaccine is critical for the control of infections associated with the RVF virus. Moreover, computational vaccine approaches are helpful in the design of specific, safe, and stable peptide-based designs when compared to the conventional methods of vaccine development. In this study, the whole proteome of the virus, comprising four proteins (NP, L, GP, and NSP), was screened to find putative vaccine epitope sequences (T cell, B cell, and HTL) specific for each protein. These shortlisted epitopes were then combined with flexible linkers to design protein-specific and proteome-wide immunogenic multi-epitope-based vaccine constructs. The results revealed that these multi-epitope vaccine constructs (MEVCs) are strongly antigenic and non-allergenic in nature. The efficacy of these constructs was further validated by docking with immune receptors, which revealed strong binding interactions with human TLR8. Using the MD simulation approach, the binding stability and residual flexibility of the best vaccine construct (proteome-wide) were confirmed, which revealed stable dynamic and favorable features. Furthermore, in-silico cloning and immune simulation analysis confirmed the expression and production of immune factors, that is, IgM, IgG, and IL-6, against the proposed vaccine designs. Additionally, 3D models of all the MEVC constructs have been developed and evaluated for potential immunization against the RVF virus. Finally, the proteome-wide vaccine candidate (MEVC-PW-RVFV) with the highest immune reinforcement potential provides new insights into the development of future vaccines against the emerging RVF virus. Frontiers Media S.A. 2022-05-31 /pmc/articles/PMC9195176/ /pubmed/35711778 http://dx.doi.org/10.3389/fmicb.2022.921683 Text en Copyright © 2022 Albutti. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Albutti, Aqel
Proteome-Wide and Protein-Specific Multi-Epitope Vaccine Constructs Against the Rift Valley Fever Virus Outbreak Using Integrated Omics Approaches
title Proteome-Wide and Protein-Specific Multi-Epitope Vaccine Constructs Against the Rift Valley Fever Virus Outbreak Using Integrated Omics Approaches
title_full Proteome-Wide and Protein-Specific Multi-Epitope Vaccine Constructs Against the Rift Valley Fever Virus Outbreak Using Integrated Omics Approaches
title_fullStr Proteome-Wide and Protein-Specific Multi-Epitope Vaccine Constructs Against the Rift Valley Fever Virus Outbreak Using Integrated Omics Approaches
title_full_unstemmed Proteome-Wide and Protein-Specific Multi-Epitope Vaccine Constructs Against the Rift Valley Fever Virus Outbreak Using Integrated Omics Approaches
title_short Proteome-Wide and Protein-Specific Multi-Epitope Vaccine Constructs Against the Rift Valley Fever Virus Outbreak Using Integrated Omics Approaches
title_sort proteome-wide and protein-specific multi-epitope vaccine constructs against the rift valley fever virus outbreak using integrated omics approaches
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9195176/
https://www.ncbi.nlm.nih.gov/pubmed/35711778
http://dx.doi.org/10.3389/fmicb.2022.921683
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