Chimeric Virus-Like Particles of Prawn Nodavirus Displaying Hepatitis B Virus Immunodominant Region: Biophysical Properties and Cytokine Response

被引：5

作者：

Ninyio, Nathaniel Nyakaat ^{[1
,2
]}

Ho, Kok Lian ^{[3
]}

Yong, Chean Yeah ^{[1
]}

Chee, Hui Yee ^{[4
]}

Hamid, Muhajir ^{[1
]}

Ong, Hui Kian ^{[3
]}

Mariatulqabtiah, Abdul Razak ^{[5
,6
]}

Tan, Wen Siang ^{[1
,6
]}

机构：

[1] Univ Putra Malaysia, Fac Biotechnol & Biomol Sci, Dept Microbiol, Seri Kembangan 43400, Selangor, Malaysia

[2] Kaduna State Univ, Fac Sci, Dept Microbiol, Pmb 2339,Tafawa Balewa Way, Kaduna 800241, Nigeria

[3] Univ Putra Malaysia, Fac Med & Hlth Sci, Dept Pathol, Seri Kembangan 43400, Selangor, Malaysia

[4] Univ Putra Malaysia, Fac Med & Hlth Sci, Dept Med Microbiol, Seri Kembangan 43400, Selangor, Malaysia

[5] Univ Putra Malaysia, Fac Biotechnol & Biomol Sci, Dept Cell & Mol Biol, Seri Kembangan 43400, Selangor, Malaysia

[6] Univ Putra Malaysia, Inst Biosci, Lab Vaccine & Biomol, Seri Kembangan 43400, Selangor, Malaysia

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2021年 / 22卷 / 04期

关键词：

prawn nodavirus; hepatitis B virus; virus-like particles; 'a' determinant; capsid protein; Sf9; cells; circular dichroism; cytokine; ELISA; MACROBRACHIUM-ROSENBERGII NODAVIRUS; IMMUNE-RESPONSES; INSECT CELLS; SURFACE; REPLICATION; IMMUNOGENICITY; EXPRESSION; ANTIBODIES; PROTEINS; VACCINE;

D O I：

10.3390/ijms22041922

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 (beta)-sheets (44.8%), and they were thermally stable up to similar to 52 degrees 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-gamma, 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 colt 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.

引用

页码：1 / 17

页数：16

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