Induction of humoral and cell-mediated immune responses by hepatitis B virus epitope displayed on the virus-like particles of prawn nodavirus

• Published in: Applied and Environmental Microbiology 2015-02, Vol.81 (3), p.882-889
• Main Authors: Yong, Chean Yeah, Yeap, Swee Keong, Goh, Zee Hong, Ho, Kok Lian, Omar, Abdul Rahman, Tan, Wen Siang
• Format: Article
• Language: English
• Subjects: Animals; Antigens; Cell Surface Display Techniques; Drug Carriers; Epitopes - genetics; Epitopes - immunology; Genetics and Molecular Biology; Hepatitis; Hepatitis B; Hepatitis B Antibodies - blood; Hepatitis B Vaccines - administration & dosage; Hepatitis B Vaccines - genetics; Hepatitis B Vaccines - immunology; Hepatitis B virus; Hepatitis B virus - genetics; Hepatitis B virus - immunology; Immunity (Disease); Interferon-gamma - secretion; Killer Cells, Natural - immunology; Macrobrachium rosenbergii; Mice, Inbred BALB C; Microbiology; Microscopy, Electron, Transmission; Nodaviridae - genetics; Nodavirus; Saccharomyces; T-Lymphocytes - immunology; Vaccines, Synthetic - administration & dosage; Vaccines, Synthetic - genetics; Vaccines, Synthetic - immunology; Vaccines, Virus-Like Particle - administration & dosage; Vaccines, Virus-Like Particle - genetics; Vaccines, Virus-Like Particle - immunology; Viruses; Yeast
• ISSN: 0099-2240; 1098-5336; 1098-6596
• DOI: 10.1128/AEM.03695-14

Hepatitis B virus (HBV) is a deadly pathogen that has killed countless people worldwide. Saccharomyces cerevisiae-derived HBV vaccines based upon hepatitis B surface antigen (HBsAg) is highly effective. However, the emergence of vaccine escape mutants due to mutations on the HBsAg and polymerase genes has produced a continuous need for the development of new HBV vaccines. In this study, the "a" determinant within HBsAg was displayed on the recombinant capsid protein of Macrobrachium rosenbergii nodavirus (MrNV), which can be purified easily in a single step through immobilized metal affinity chromatography (IMAC). The purified protein self-assembled into virus-like particles (VLPs) when observed under a transmission electron microscope (TEM). Immunization of BALB/c mice with this chimeric protein induced specific antibodies against the "a" determinant. In addition, it induced significantly more natural killer and cytotoxic T cells, as well as an increase in interferon gamma (IFN-γ) secretion, which are vital for virus clearance. Collectively, these findings demonstrated that the MrNV capsid protein is a potential carrier for the HBV "a" determinant, which can be further extended to display other foreign epitopes. This paper is the first to report the application of MrNV VLPs as a novel platform to display foreign epitopes.