Chimeric virus-like particles of prawn nodavirus displaying hepatitis B virus immunodominant region: biophysical properties and cytokine response
Hepatitis B is a major global health challenge. In the absence of an effective treatment for the disease, hepatitis B vaccines provide protection against the viral infection. However, some individuals do not have positive immune responses after being vaccinated with the hepatitis B vaccines availabl...
| Main Authors: | , , , , , , , |
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| Format: | Article |
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Multidisciplinary Digital Publishing Institute
2021
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| _version_ | 1825937705213624320 |
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| author | Ninyio, Nathaniel Nyakaat Ho, Kok Lian Yong, Chean Yeah Chee, Hui Yee Hamid, Muhajir Ong, Hui Kian Abdul Razak, Mariatulqabtiah Tan, Wen Siang |
| author_facet | Ninyio, Nathaniel Nyakaat Ho, Kok Lian Yong, Chean Yeah Chee, Hui Yee Hamid, Muhajir Ong, Hui Kian Abdul Razak, Mariatulqabtiah Tan, Wen Siang |
| author_sort | Ninyio, Nathaniel Nyakaat |
| collection | UPM |
| description | Hepatitis B is a major global health challenge. In the absence of an effective treatment for the disease, hepatitis B vaccines provide protection against the viral infection. However, some individuals do not have positive immune responses after being vaccinated with the hepatitis B vaccines available in the market. Thus, it is important to develop a more protective vaccine. Previously, we showed that hepatitis B virus (HBV) ‘a’ determinant (aD) displayed on the prawn nodavirus capsid (Nc) and expressed in Spodoptera frugiperda (Sf9) cells (namely, Nc-aD-Sf9) self-assembled into virus-like particles (VLPs). Immunisation of BALB/c mice with the Nc-aD-Sf9 VLPs showed significant induction of humoral, cellular and memory B-cell immunity. In the present study, the biophysical properties of the Nc-aD-Sf9 VLPs were studied using dynamic light scattering (DLS) and circular dichroism (CD) spectroscopy. Enzyme-linked immunosorbent assay (ELISA) was used to determine the antigenicity of the Nc-aD-Sf9 VLPs, and multiplex ELISA was employed to quantify the cytokine response induced by the VLPs administered intramuscularly into BALB/c mice (n = 8). CD spectroscopy of Nc-aD-Sf9 VLPs showed that the secondary structure of the VLPs predominantly consisted of beta (β)-sheets (44.8%), and they were thermally stable up to ~52 °C. ELISA revealed that the aD epitope of the VLPs was significantly antigenic to anti-HBV surface antigen (HBsAg) antibodies. In addition, multiplex ELISA of serum samples from the vaccinated mice showed a significant induction (p < 0.001) of IFN-γ, IL-4, IL-5, IL-6, IL-10, and IL-12p70. This cytokine profile is indicative of natural killer cell, macrophage, dendritic cell and cytotoxic T-lymphocyte activities, which suggests a prophylactic innate and adaptive cellular immune response mediated by Nc-aD-Sf9 VLPs. Interestingly, Nc-aD-Sf9 induced a more robust release of the aforementioned cytokines than that of Nc-aD VLPs produced in Escherichia coli and a commercially used hepatitis B vaccine. Overall, Nc-aD-Sf9 VLPs are thermally stable and significantly antigenic, demonstrating their potential as an HBV vaccine candidate. |
| first_indexed | 2024-03-06T11:03:34Z |
| format | Article |
| id | upm.eprints-96387 |
| institution | Universiti Putra Malaysia |
| last_indexed | 2024-03-06T11:03:34Z |
| publishDate | 2021 |
| publisher | Multidisciplinary Digital Publishing Institute |
| record_format | dspace |
| spelling | upm.eprints-963872023-01-26T07:59:37Z http://psasir.upm.edu.my/id/eprint/96387/ Chimeric virus-like particles of prawn nodavirus displaying hepatitis B virus immunodominant region: biophysical properties and cytokine response Ninyio, Nathaniel Nyakaat Ho, Kok Lian Yong, Chean Yeah Chee, Hui Yee Hamid, Muhajir Ong, Hui Kian Abdul Razak, Mariatulqabtiah Tan, Wen Siang Hepatitis B is a major global health challenge. In the absence of an effective treatment for the disease, hepatitis B vaccines provide protection against the viral infection. However, some individuals do not have positive immune responses after being vaccinated with the hepatitis B vaccines available in the market. Thus, it is important to develop a more protective vaccine. Previously, we showed that hepatitis B virus (HBV) ‘a’ determinant (aD) displayed on the prawn nodavirus capsid (Nc) and expressed in Spodoptera frugiperda (Sf9) cells (namely, Nc-aD-Sf9) self-assembled into virus-like particles (VLPs). Immunisation of BALB/c mice with the Nc-aD-Sf9 VLPs showed significant induction of humoral, cellular and memory B-cell immunity. In the present study, the biophysical properties of the Nc-aD-Sf9 VLPs were studied using dynamic light scattering (DLS) and circular dichroism (CD) spectroscopy. Enzyme-linked immunosorbent assay (ELISA) was used to determine the antigenicity of the Nc-aD-Sf9 VLPs, and multiplex ELISA was employed to quantify the cytokine response induced by the VLPs administered intramuscularly into BALB/c mice (n = 8). CD spectroscopy of Nc-aD-Sf9 VLPs showed that the secondary structure of the VLPs predominantly consisted of beta (β)-sheets (44.8%), and they were thermally stable up to ~52 °C. ELISA revealed that the aD epitope of the VLPs was significantly antigenic to anti-HBV surface antigen (HBsAg) antibodies. In addition, multiplex ELISA of serum samples from the vaccinated mice showed a significant induction (p < 0.001) of IFN-γ, IL-4, IL-5, IL-6, IL-10, and IL-12p70. This cytokine profile is indicative of natural killer cell, macrophage, dendritic cell and cytotoxic T-lymphocyte activities, which suggests a prophylactic innate and adaptive cellular immune response mediated by Nc-aD-Sf9 VLPs. Interestingly, Nc-aD-Sf9 induced a more robust release of the aforementioned cytokines than that of Nc-aD VLPs produced in Escherichia coli and a commercially used hepatitis B vaccine. Overall, Nc-aD-Sf9 VLPs are thermally stable and significantly antigenic, demonstrating their potential as an HBV vaccine candidate. Multidisciplinary Digital Publishing Institute 2021 Article PeerReviewed Ninyio, Nathaniel Nyakaat and Ho, Kok Lian and Yong, Chean Yeah and Chee, Hui Yee and Hamid, Muhajir and Ong, Hui Kian and Abdul Razak, Mariatulqabtiah and Tan, Wen Siang (2021) Chimeric virus-like particles of prawn nodavirus displaying hepatitis B virus immunodominant region: biophysical properties and cytokine response. International Journal of Molecular Sciences, 22 (4). pp. 1-16. ISSN 1661-6596; ESSN: 1422-0067 https://www.mdpi.com/1422-0067/22/4/1922 10.3390/ijms22041922 |
| spellingShingle | Ninyio, Nathaniel Nyakaat Ho, Kok Lian Yong, Chean Yeah Chee, Hui Yee Hamid, Muhajir Ong, Hui Kian Abdul Razak, Mariatulqabtiah Tan, Wen Siang Chimeric virus-like particles of prawn nodavirus displaying hepatitis B virus immunodominant region: biophysical properties and cytokine response |
| title | Chimeric virus-like particles of prawn nodavirus displaying hepatitis B virus immunodominant region: biophysical properties and cytokine response |
| title_full | Chimeric virus-like particles of prawn nodavirus displaying hepatitis B virus immunodominant region: biophysical properties and cytokine response |
| title_fullStr | Chimeric virus-like particles of prawn nodavirus displaying hepatitis B virus immunodominant region: biophysical properties and cytokine response |
| title_full_unstemmed | Chimeric virus-like particles of prawn nodavirus displaying hepatitis B virus immunodominant region: biophysical properties and cytokine response |
| title_short | Chimeric virus-like particles of prawn nodavirus displaying hepatitis B virus immunodominant region: biophysical properties and cytokine response |
| title_sort | chimeric virus like particles of prawn nodavirus displaying hepatitis b virus immunodominant region biophysical properties and cytokine response |
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