Yong Chean Yeah, Yeap Swee Keong, Goh Zee Hong, Ho Kok Lian, Omar Abdul Rahman, Tan Wen Siang
Department of Microbiology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia.
Institute of Bioscience, Universiti Putra Malaysia, Serdang, Selangor, Malaysia.
Appl Environ Microbiol. 2015 Feb;81(3):882-9. doi: 10.1128/AEM.03695-14. Epub 2014 Nov 21.
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.
乙型肝炎病毒(HBV)是一种致命病原体,已在全球造成无数人死亡。基于乙型肝炎表面抗原(HBsAg)的啤酒酵母衍生的HBV疫苗非常有效。然而,由于HBsAg和聚合酶基因上的突变导致疫苗逃逸突变体的出现,持续需要开发新的HBV疫苗。在本研究中,HBsAg内的“a”决定簇展示在罗氏沼虾诺达病毒(MrNV)的重组衣壳蛋白上,该蛋白可通过固定化金属亲和色谱(IMAC)一步轻松纯化。在透射电子显微镜(TEM)下观察时,纯化的蛋白自组装成病毒样颗粒(VLP)。用这种嵌合蛋白免疫BALB/c小鼠可诱导针对“a”决定簇的特异性抗体。此外,它诱导产生显著更多的自然杀伤细胞和细胞毒性T细胞,以及干扰素γ(IFN-γ)分泌增加,这些对于病毒清除至关重要。总体而言,这些发现表明MrNV衣壳蛋白是HBV“a”决定簇的潜在载体,可进一步扩展以展示其他外来表位。本文首次报道了MrNV VLP作为展示外来表位的新型平台的应用。