Immunoinformatics-driven design of a multi-epitope vaccine targeting neonatal rotavirus with focus on outer capsid proteins VP4 and VP7 and non structural proteins NSP2 and NSP5

Abstract Rotaviral gastroenteritis remains a major global health concern, particularly for infants and young children under five years old. Prior to the introduction of the WHO-prequalified rotavirus vaccine, rotavirus (RV) was responsible for approximately 800,000 child deaths annually in developin...

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Main Authors: Arijit Das Sharma, Jorge Samuel Leon Magdaleno, Himanshu Singh, Andrés Felipe Cuspoca Orduz, Luigi Cavallo, Mohit Chawla
Format: Article
Language:English
Published: Nature Portfolio 2025-04-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-95256-8
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author Arijit Das Sharma
Jorge Samuel Leon Magdaleno
Himanshu Singh
Andrés Felipe Cuspoca Orduz
Luigi Cavallo
Mohit Chawla
author_facet Arijit Das Sharma
Jorge Samuel Leon Magdaleno
Himanshu Singh
Andrés Felipe Cuspoca Orduz
Luigi Cavallo
Mohit Chawla
author_sort Arijit Das Sharma
collection DOAJ
description Abstract Rotaviral gastroenteritis remains a major global health concern, particularly for infants and young children under five years old. Prior to the introduction of the WHO-prequalified rotavirus vaccine, rotavirus (RV) was responsible for approximately 800,000 child deaths annually in developing countries. Although vaccination efforts have reduced this number, RV still causes around 200,000 child deaths each year worldwide. The current WHO-prequalified vaccines are live attenuated and offer limited efficacy of 40–60%, with a slight risk of intussusception in young children. To overcome these limitations, we employed immunoinformatics to design a novel multi-epitope vaccine (MEV) targeting rotavirus outer capsid proteins VP4 and VP7, as well as crucial non-structural proteins NSP2 and NSP5. The RV-MEV incorporates 10 epitopes, including 4 CD8 + T-cell, 5 CD4 + T-cell, and 1 B-cell epitope, all of which are antigenic, non-allergenic, and non-toxic. These epitopes also showed potential to induce interferon-γ (IFN-γ). Molecular simulation studies confirmed stable interactions between RV-MEV and human TLR5 and integrin αvβ5 complexes. The RV-MEV was successfully cloned into a pET28a(+) vector during in-silico cloning. Immune simulation studies predict a strong immune response to the RV-MEV. Future in vitro and in vivo studies are necessary to validate the vaccine’s effectiveness in providing protection against various rotavirus strains in neonates.
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spelling doaj-art-79fe9efcfa914e4abc0fe06cd551235d2025-08-20T03:10:07ZengNature PortfolioScientific Reports2045-23222025-04-0115112410.1038/s41598-025-95256-8Immunoinformatics-driven design of a multi-epitope vaccine targeting neonatal rotavirus with focus on outer capsid proteins VP4 and VP7 and non structural proteins NSP2 and NSP5Arijit Das Sharma0Jorge Samuel Leon Magdaleno1Himanshu Singh2Andrés Felipe Cuspoca Orduz3Luigi Cavallo4Mohit Chawla5School of Bio-Engineering and Bio-Sciences, Lovely Professional UniversityPhysical Sciences and Engineering Division, Kaust Catalysis Center, King Abdullah University of Science and Technology (KAUST)School of Bio-Engineering and Bio-Sciences, Lovely Professional UniversityGupo de Investigación en Epidemiología Clínica de Colombia (GRECO), Universidad Pedagógica y Tecnológica de ColombiaPhysical Sciences and Engineering Division, Kaust Catalysis Center, King Abdullah University of Science and Technology (KAUST)Physical Sciences and Engineering Division, Kaust Catalysis Center, King Abdullah University of Science and Technology (KAUST)Abstract Rotaviral gastroenteritis remains a major global health concern, particularly for infants and young children under five years old. Prior to the introduction of the WHO-prequalified rotavirus vaccine, rotavirus (RV) was responsible for approximately 800,000 child deaths annually in developing countries. Although vaccination efforts have reduced this number, RV still causes around 200,000 child deaths each year worldwide. The current WHO-prequalified vaccines are live attenuated and offer limited efficacy of 40–60%, with a slight risk of intussusception in young children. To overcome these limitations, we employed immunoinformatics to design a novel multi-epitope vaccine (MEV) targeting rotavirus outer capsid proteins VP4 and VP7, as well as crucial non-structural proteins NSP2 and NSP5. The RV-MEV incorporates 10 epitopes, including 4 CD8 + T-cell, 5 CD4 + T-cell, and 1 B-cell epitope, all of which are antigenic, non-allergenic, and non-toxic. These epitopes also showed potential to induce interferon-γ (IFN-γ). Molecular simulation studies confirmed stable interactions between RV-MEV and human TLR5 and integrin αvβ5 complexes. The RV-MEV was successfully cloned into a pET28a(+) vector during in-silico cloning. Immune simulation studies predict a strong immune response to the RV-MEV. Future in vitro and in vivo studies are necessary to validate the vaccine’s effectiveness in providing protection against various rotavirus strains in neonates.https://doi.org/10.1038/s41598-025-95256-8RotavirusGastroenteritisNeonatesImmunoinformaticsImmune simulationToll-like receptors (TLRs)
spellingShingle Arijit Das Sharma
Jorge Samuel Leon Magdaleno
Himanshu Singh
Andrés Felipe Cuspoca Orduz
Luigi Cavallo
Mohit Chawla
Immunoinformatics-driven design of a multi-epitope vaccine targeting neonatal rotavirus with focus on outer capsid proteins VP4 and VP7 and non structural proteins NSP2 and NSP5
Scientific Reports
Rotavirus
Gastroenteritis
Neonates
Immunoinformatics
Immune simulation
Toll-like receptors (TLRs)
title Immunoinformatics-driven design of a multi-epitope vaccine targeting neonatal rotavirus with focus on outer capsid proteins VP4 and VP7 and non structural proteins NSP2 and NSP5
title_full Immunoinformatics-driven design of a multi-epitope vaccine targeting neonatal rotavirus with focus on outer capsid proteins VP4 and VP7 and non structural proteins NSP2 and NSP5
title_fullStr Immunoinformatics-driven design of a multi-epitope vaccine targeting neonatal rotavirus with focus on outer capsid proteins VP4 and VP7 and non structural proteins NSP2 and NSP5
title_full_unstemmed Immunoinformatics-driven design of a multi-epitope vaccine targeting neonatal rotavirus with focus on outer capsid proteins VP4 and VP7 and non structural proteins NSP2 and NSP5
title_short Immunoinformatics-driven design of a multi-epitope vaccine targeting neonatal rotavirus with focus on outer capsid proteins VP4 and VP7 and non structural proteins NSP2 and NSP5
title_sort immunoinformatics driven design of a multi epitope vaccine targeting neonatal rotavirus with focus on outer capsid proteins vp4 and vp7 and non structural proteins nsp2 and nsp5
topic Rotavirus
Gastroenteritis
Neonates
Immunoinformatics
Immune simulation
Toll-like receptors (TLRs)
url https://doi.org/10.1038/s41598-025-95256-8
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