Immunological Analysis of Nodavirus Capsid Displaying the Domain III of Japanese Encephalitis Virus Envelope Protein

Japanese encephalitis virus (JEV) is the pathogen that causes Japanese encephalitis (JE) in humans and horses. Lethality of the virus was reported to be between 20–30%, of which, 30–50% of the JE survivors develop neurological and psychiatric sequelae. Attributed to the low effectiveness of current...

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Autores principales: Kiven Kumar, Hui Kian Ong, Wen Siang Tan, Siti Suri Arshad, Kok Lian Ho
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Publicado: MDPI AG 2021
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Acceso en línea:https://doaj.org/article/6093cb2ee0c54c09ad9546c9ad49709e
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spelling oai:doaj.org-article:6093cb2ee0c54c09ad9546c9ad49709e2021-11-25T18:40:59ZImmunological Analysis of Nodavirus Capsid Displaying the Domain III of Japanese Encephalitis Virus Envelope Protein10.3390/pharmaceutics131118261999-4923https://doaj.org/article/6093cb2ee0c54c09ad9546c9ad49709e2021-11-01T00:00:00Zhttps://www.mdpi.com/1999-4923/13/11/1826https://doaj.org/toc/1999-4923Japanese encephalitis virus (JEV) is the pathogen that causes Japanese encephalitis (JE) in humans and horses. Lethality of the virus was reported to be between 20–30%, of which, 30–50% of the JE survivors develop neurological and psychiatric sequelae. Attributed to the low effectiveness of current therapeutic approaches against JEV, vaccination remains the only effective approach to prevent the viral infection. Currently, live-attenuated and chimeric-live vaccines are widely used worldwide but these vaccines pose a risk of virulence restoration. Therefore, continuing development of JE vaccines with higher safety profiles and better protective efficacies is urgently needed. In this study, the <i>Macrobrachium rosenbergii</i> nodavirus (<i>Mr</i>NV) capsid protein (CP) fused with the domain III of JEV envelope protein (JEV-DIII) was produced in <i>Escherichia coli</i>. The fusion protein (<i>Mr</i>NV-CP<sup>JEV-DIII</sup>) assembled into virus-like particles (VLPs) with a diameter of approximately 18 nm. The BALB/c mice injected with the VLPs alone or in the presence of alum successfully elicited the production of anti-JEV-DIII antibody, with titers significantly higher than that in mice immunized with IMOJEV, a commercially available vaccine. Immunophenotyping showed that the <i>Mr</i>NV-CP<sup>JEV-DIII</sup> supplemented with alum triggered proliferation of cytotoxic T-lymphocytes, macrophages, and natural killer (NK) cells. Additionally, cytokine profiles of the immunized mice revealed activities of cytotoxic T-lymphocytes, macrophages, and NK cells, indicating the activation of adaptive cellular and innate immune responses mediated by <i>Mr</i>NV-CP<sup>JEV-DIII</sup> VLPs. Induction of innate, humoral, and cellular immune responses by the <i>Mr</i>NV-CP<sup>JEV-DIII</sup> VLPs suggest that the chimeric protein is a promising JEV vaccine candidate.Kiven KumarHui Kian OngWen Siang TanSiti Suri ArshadKok Lian HoMDPI AGarticleJapanese encephalitis vaccine<i>Macrobrachium rosenbergii</i> nodavirusvirus-like particles (VLP)domain IIIcytokinescytotoxic T-lymphocytesPharmacy and materia medicaRS1-441ENPharmaceutics, Vol 13, Iss 1826, p 1826 (2021)
institution DOAJ
collection DOAJ
language EN
topic Japanese encephalitis vaccine
<i>Macrobrachium rosenbergii</i> nodavirus
virus-like particles (VLP)
domain III
cytokines
cytotoxic T-lymphocytes
Pharmacy and materia medica
RS1-441
spellingShingle Japanese encephalitis vaccine
<i>Macrobrachium rosenbergii</i> nodavirus
virus-like particles (VLP)
domain III
cytokines
cytotoxic T-lymphocytes
Pharmacy and materia medica
RS1-441
Kiven Kumar
Hui Kian Ong
Wen Siang Tan
Siti Suri Arshad
Kok Lian Ho
Immunological Analysis of Nodavirus Capsid Displaying the Domain III of Japanese Encephalitis Virus Envelope Protein
description Japanese encephalitis virus (JEV) is the pathogen that causes Japanese encephalitis (JE) in humans and horses. Lethality of the virus was reported to be between 20–30%, of which, 30–50% of the JE survivors develop neurological and psychiatric sequelae. Attributed to the low effectiveness of current therapeutic approaches against JEV, vaccination remains the only effective approach to prevent the viral infection. Currently, live-attenuated and chimeric-live vaccines are widely used worldwide but these vaccines pose a risk of virulence restoration. Therefore, continuing development of JE vaccines with higher safety profiles and better protective efficacies is urgently needed. In this study, the <i>Macrobrachium rosenbergii</i> nodavirus (<i>Mr</i>NV) capsid protein (CP) fused with the domain III of JEV envelope protein (JEV-DIII) was produced in <i>Escherichia coli</i>. The fusion protein (<i>Mr</i>NV-CP<sup>JEV-DIII</sup>) assembled into virus-like particles (VLPs) with a diameter of approximately 18 nm. The BALB/c mice injected with the VLPs alone or in the presence of alum successfully elicited the production of anti-JEV-DIII antibody, with titers significantly higher than that in mice immunized with IMOJEV, a commercially available vaccine. Immunophenotyping showed that the <i>Mr</i>NV-CP<sup>JEV-DIII</sup> supplemented with alum triggered proliferation of cytotoxic T-lymphocytes, macrophages, and natural killer (NK) cells. Additionally, cytokine profiles of the immunized mice revealed activities of cytotoxic T-lymphocytes, macrophages, and NK cells, indicating the activation of adaptive cellular and innate immune responses mediated by <i>Mr</i>NV-CP<sup>JEV-DIII</sup> VLPs. Induction of innate, humoral, and cellular immune responses by the <i>Mr</i>NV-CP<sup>JEV-DIII</sup> VLPs suggest that the chimeric protein is a promising JEV vaccine candidate.
format article
author Kiven Kumar
Hui Kian Ong
Wen Siang Tan
Siti Suri Arshad
Kok Lian Ho
author_facet Kiven Kumar
Hui Kian Ong
Wen Siang Tan
Siti Suri Arshad
Kok Lian Ho
author_sort Kiven Kumar
title Immunological Analysis of Nodavirus Capsid Displaying the Domain III of Japanese Encephalitis Virus Envelope Protein
title_short Immunological Analysis of Nodavirus Capsid Displaying the Domain III of Japanese Encephalitis Virus Envelope Protein
title_full Immunological Analysis of Nodavirus Capsid Displaying the Domain III of Japanese Encephalitis Virus Envelope Protein
title_fullStr Immunological Analysis of Nodavirus Capsid Displaying the Domain III of Japanese Encephalitis Virus Envelope Protein
title_full_unstemmed Immunological Analysis of Nodavirus Capsid Displaying the Domain III of Japanese Encephalitis Virus Envelope Protein
title_sort immunological analysis of nodavirus capsid displaying the domain iii of japanese encephalitis virus envelope protein
publisher MDPI AG
publishDate 2021
url https://doaj.org/article/6093cb2ee0c54c09ad9546c9ad49709e
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AT sitisuriarshad immunologicalanalysisofnodaviruscapsiddisplayingthedomainiiiofjapaneseencephalitisvirusenvelopeprotein
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