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-␥) 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.
Hepatitis B virus (HBV) is a partially double-stranded DNA virus that belongs to the family Hepadnaviridae. It is known to be the major cause of liver-associated diseases, including liver cirrhosis and hepatocellular carcinoma. Approximately 2 billion people worldwide have been infected by HBV, among which about 350 million chronically infected people serve as a reservoir for the virus (1, 2). To date, there is no effective treatment for HBV infection despite intensive studies on antiviral drugs. Thus, preventive measures, including immunization with HBV vaccine, remain necessary.HBV surface antigens (HBsAg) purified from the sera of infected patients have been used for immunization against HBV infection since 1981. The full-length HBsAg gene has three different start codons and a common stop codon and encodes HBsAg of different lengths (3). The longest is the large HBsAg (L-HBsAg), followed by the middle HBsAg (M-HBsAg), and the smallest is the small HBsAg (S-HBsAg). L-HBsAg is composed of 389 or 400 amino acids (aa), depending on the virus genotypes. It contains the pre-S1 region (108 or 119 aa), followed by the pre-S2 region (55 aa) and S-HBsAg (226 aa). The N-terminal end of M-HBsAg harbors the pre-S2 region at its S-HBsAg. The S-HBsAg contains 226 aa in the absence of the pre-S1 and pre-S2 regions.The HBsAg in serum self-assemble into noninfectious 22-nm spherical or filamentous particles, along with lipid components (4), which are capable of inducing neutralizing antibodies against HBV infection. Although highly effective, the use of plasma-derived HBsAg for vaccination is limited by the production cost, as well as the possibility of contamination by other infectious pathogens present in...