Abstract
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.
Highlights
More recent advances in vaccinology have extensively exploited virus-like particles (VLPs) as effective entities for use in vaccine delivery
nodavirus capsid (Nc)-a’ determinant (aD) VLPs produced in the insect Sf9 cells showed ~3.8-fold higher yield than those produced in E. coli, suggesting that Sf9 cells are a better expression system for Nc-aD
Enzyme-Linked Immunosorbent Assay (ELISA) revealed that the aD component of the Nc-aD VLPs was antigenic to anti-HBV surface antigen (HBsAg) antibodies indicating no suppression of aD’s antigenicity after fusion to Nc
Summary
More recent advances in vaccinology have extensively exploited virus-like particles (VLPs) as effective entities for use in vaccine delivery. Some viral antigens have been displayed on VLPs to enhance the immunogenicity of the antigens [1]. The resultant chimeric VLPs usually consist of multiple copies of a viral structural protein displaying the immunogenic epitope [1]. The VLPs of Macrobrachium rosenbergii nodavirus (MrNV). Have previously been employed as nanocarriers to display immunogenic viral epitopes of hepatitis B virus (HBV) and human influenza A virus (IAV) [1,2]. MrNV is a non-enveloped RNA virus of the family Nodaviridae [3,4]. Its RNA genome consists of two single-stranded RNA molecules known as RNA1 and RNA2.
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