Yin Ying, Zhang Jun, Dong Dayong, Liu Shuling, Guo Qiang, Song Xiaohong, Li Guanlin, Fu Ling, Xu Junjie, Chen Wei
State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, 20 Dongdajie, Fengtai, Beijing 100071, China.
Vaccine. 2008 Oct 29;26(46):5814-21. doi: 10.1016/j.vaccine.2008.08.031. Epub 2008 Sep 9.
The major aim of present study is to develop and evaluate chimeric virus-like particles (VLPs) displaying a neutralizing epitope of anthrax protective antigen (PA) as a potential vaccine against anthrax. The truncated hepatitis B virus core (HBc) protein (aa 1-144) was used as a carrier, and the 2beta2-2beta3 loop of the PA domain 2 (aa 302-325) which has been shown contains a dominant neutralizing epitope was inserted into the major immunodominant region (MIR) of the HBc. The recombinant protein HBc-N144-PA-loop2 was expressed in Escherichia coli, and was able to form HBc-like particles confirmed by electron microscopy. The immunogenicity of these chimeric particles was evaluated in mice and guinea pigs. In mice the HBc-N144-PA-loop2 was able to induce PA-epitope specific antibodies; in guinea pigs it was able to induce PA-epitope specific antibodies and anthrax toxin-neutralizing antibodies regardless of whether alum adjuvant was used or not, and was able to partially protect the immunized guinea pigs against virulent anthrax spores challenge. This study suggests chimeric HBc particles carrying a neutralizing epitope of PA can induce protective immunity against Bacillus anthracis.
本研究的主要目的是开发和评估展示炭疽保护性抗原（PA）中和表位的嵌合病毒样颗粒（VLP）作为一种潜在的炭疽疫苗。截短的乙型肝炎病毒核心（HBc）蛋白（氨基酸1 - 144）用作载体，将已显示含有主要中和表位的PA结构域2的2β2 - 2β3环（氨基酸302 - 325）插入HBc的主要免疫显性区域（MIR）。重组蛋白HBc - N144 - PA - loop2在大肠杆菌中表达，并通过电子显微镜证实能够形成HBc样颗粒。在小鼠和豚鼠中评估了这些嵌合颗粒的免疫原性。在小鼠中，HBc - N144 - PA - loop2能够诱导PA表位特异性抗体；在豚鼠中，无论是否使用明矾佐剂，它都能够诱导PA表位特异性抗体和炭疽毒素中和抗体，并且能够部分保护免疫的豚鼠免受强毒炭疽芽孢攻击。本研究表明携带PA中和表位的嵌合HBc颗粒可诱导针对炭疽芽孢杆菌的保护性免疫。
