Immunoinformatics method to design universal multi-epitope nanoparticle vaccine for TGEV S protein

Abstract Porcine transmissible enteritis virus (TGEV) is a fatal pathogen affecting newborn piglets, presenting a significant challenge to global intensive pig farming biosecurity due to its ongoing mutation. There is still a lack of effective vaccines to combat this virus, Vaccination has long been...

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Main Authors: Shinian Li, Jingjing Yu, Chencheng Xiao, Yaling Li
Format: Article
Language:English
Published: Nature Portfolio 2025-03-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-95602-w
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author Shinian Li
Jingjing Yu
Chencheng Xiao
Yaling Li
author_facet Shinian Li
Jingjing Yu
Chencheng Xiao
Yaling Li
author_sort Shinian Li
collection DOAJ
description Abstract Porcine transmissible enteritis virus (TGEV) is a fatal pathogen affecting newborn piglets, presenting a significant challenge to global intensive pig farming biosecurity due to its ongoing mutation. There is still a lack of effective vaccines to combat this virus, Vaccination has long been considered the most effective way to overcome infectious diseases, however, traditional vaccines cannot be brought to market quickly enough to deal with rapid mutations and emerging viruses. Therefore, this study addresses this gap by using immunoinformatics methods and ferritin nanoparticle delivery system to build a platform for rapid research and development of porcine coronavirus vaccine, designing a candidate nanoparticle vaccine that targets the TGEV S protein. To this end, multiple servers and strict screening criteria were used to analyze the S protein, and 3 CTL dominant epitopes, 3 Th dominant epitopes, and 6 B cell dominant epitopes were obtained. The candidate nanoparticle vaccine was constructed by incorporating ferritin sequences through the C-terminus after they were tandemly linked in a certain order using a flexible linker. Further experimental analyses showed that the designed candidate nanoparticle vaccine possessed relatively high antigenicity, immunogenicity, non-allergenicity, non-transmembrane proteins, suitable physicochemical properties, and high solubility upon overexpression. Tertiary structure modeling and disulfide engineering ensured conformational similarity to natural proteins and high stability. Additionally, the model predicted 6 Linear Epitopes and 6 Discontinuous Epitopes for B-cell conformational epitopes. Docking with TLR-3 and TLR-4 molecules shows a large number of interacting hydrogen-bonded amino acid residues and hydrophobically interacting amino acid residues. Immunomimetic assays show high levels of immunoglobulin, T-lymphocyte and IFN-γ secretion and may elicit specific immune responses. Through computerized cloning, the candidate nanoparticle vaccine can be efficiently expressed in the E. coli K12 expression system, aligning with future large-scale industrial production strategies. Overall, the results indicate that the constructed candidate nanoparticle vaccine can be effectively expressed and may be able to induce a strong immune response, which is expected to be an ideal candidate vaccine against TGEV.
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spelling doaj-art-c5fac35eb7c0429ea62fd2ca55f5e2f62025-08-20T02:49:32ZengNature PortfolioScientific Reports2045-23222025-03-0115111510.1038/s41598-025-95602-wImmunoinformatics method to design universal multi-epitope nanoparticle vaccine for TGEV S proteinShinian Li0Jingjing Yu1Chencheng Xiao2Yaling Li3College of Animal Science and Technology & College of Veterinary Medicine of Zhejiang, A&F UniversityCollege of Animal Science and Technology, Shihezi UniversityCollege of Animal Science and Technology, Shihezi UniversityCollege of Animal Science and Technology & College of Veterinary Medicine of Zhejiang, A&F UniversityAbstract Porcine transmissible enteritis virus (TGEV) is a fatal pathogen affecting newborn piglets, presenting a significant challenge to global intensive pig farming biosecurity due to its ongoing mutation. There is still a lack of effective vaccines to combat this virus, Vaccination has long been considered the most effective way to overcome infectious diseases, however, traditional vaccines cannot be brought to market quickly enough to deal with rapid mutations and emerging viruses. Therefore, this study addresses this gap by using immunoinformatics methods and ferritin nanoparticle delivery system to build a platform for rapid research and development of porcine coronavirus vaccine, designing a candidate nanoparticle vaccine that targets the TGEV S protein. To this end, multiple servers and strict screening criteria were used to analyze the S protein, and 3 CTL dominant epitopes, 3 Th dominant epitopes, and 6 B cell dominant epitopes were obtained. The candidate nanoparticle vaccine was constructed by incorporating ferritin sequences through the C-terminus after they were tandemly linked in a certain order using a flexible linker. Further experimental analyses showed that the designed candidate nanoparticle vaccine possessed relatively high antigenicity, immunogenicity, non-allergenicity, non-transmembrane proteins, suitable physicochemical properties, and high solubility upon overexpression. Tertiary structure modeling and disulfide engineering ensured conformational similarity to natural proteins and high stability. Additionally, the model predicted 6 Linear Epitopes and 6 Discontinuous Epitopes for B-cell conformational epitopes. Docking with TLR-3 and TLR-4 molecules shows a large number of interacting hydrogen-bonded amino acid residues and hydrophobically interacting amino acid residues. Immunomimetic assays show high levels of immunoglobulin, T-lymphocyte and IFN-γ secretion and may elicit specific immune responses. Through computerized cloning, the candidate nanoparticle vaccine can be efficiently expressed in the E. coli K12 expression system, aligning with future large-scale industrial production strategies. Overall, the results indicate that the constructed candidate nanoparticle vaccine can be effectively expressed and may be able to induce a strong immune response, which is expected to be an ideal candidate vaccine against TGEV.https://doi.org/10.1038/s41598-025-95602-wTransmissible gastroenteritis virusSpike proteinImmunoinformaticsDominant epitopeFerritinNanoparticle vaccine
spellingShingle Shinian Li
Jingjing Yu
Chencheng Xiao
Yaling Li
Immunoinformatics method to design universal multi-epitope nanoparticle vaccine for TGEV S protein
Scientific Reports
Transmissible gastroenteritis virus
Spike protein
Immunoinformatics
Dominant epitope
Ferritin
Nanoparticle vaccine
title Immunoinformatics method to design universal multi-epitope nanoparticle vaccine for TGEV S protein
title_full Immunoinformatics method to design universal multi-epitope nanoparticle vaccine for TGEV S protein
title_fullStr Immunoinformatics method to design universal multi-epitope nanoparticle vaccine for TGEV S protein
title_full_unstemmed Immunoinformatics method to design universal multi-epitope nanoparticle vaccine for TGEV S protein
title_short Immunoinformatics method to design universal multi-epitope nanoparticle vaccine for TGEV S protein
title_sort immunoinformatics method to design universal multi epitope nanoparticle vaccine for tgev s protein
topic Transmissible gastroenteritis virus
Spike protein
Immunoinformatics
Dominant epitope
Ferritin
Nanoparticle vaccine
url https://doi.org/10.1038/s41598-025-95602-w
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AT yalingli immunoinformaticsmethodtodesignuniversalmultiepitopenanoparticlevaccinefortgevsprotein