Beesley K M, Francis M J, Clarke B E, Beesley J E, Dopping-Hepenstal P J, Clare J J, Brown F, Romanos M A
Department of Molecular Biology and Virology, Wellcome Research Laboratories, Beckenham, Kent.
Biotechnology (N Y). 1990 Jul;8(7):644-9. doi: 10.1038/nbt0790-644.
Hepatitis B core protein (HBcAg) is a potent antigen that gives both a T-cell-dependent and a T-cell-independent antibody response. It has been shown that a foreign epitope can be fused to the amino terminus of HBcAg without affecting particle integrity, and that the resulting chimaeric cores retain the immunogenicity of the foreign epitope. Here we describe the efficient expression in yeast of two different chimaeric cores, carrying epitopes of Foot and Mouth Disease Virus (FMDV) or human chorionic gonadotrophin (hCG), which are candidates for FMD and contraceptive vaccines, respectively. These cores could not be produced in E. coli in soluble form but were expressed to high levels in yeast. We constructed a yeast expression vector that allows rapid production of different chimaeric cores by cloning in cassettes encoding foreign epitopes. Both FMDV and hCG-cores were shown to present the epitopes at the surface of the particles. The FMDV-cores produced in yeast were efficient inducers of neutralising antibodies in guinea-pigs after one low dose.
乙肝核心蛋白（HBcAg）是一种强效抗原，能引发T细胞依赖性和T细胞非依赖性抗体反应。研究表明，一个外源表位可以融合到HBcAg的氨基末端而不影响颗粒的完整性，并且由此产生的嵌合核心保留了外源表位的免疫原性。在此，我们描述了两种不同嵌合核心在酵母中的高效表达，它们分别携带口蹄疫病毒（FMDV）或人绒毛膜促性腺激素（hCG）的表位，分别作为口蹄疫疫苗和避孕疫苗的候选物。这些核心不能以可溶形式在大肠杆菌中产生，但在酵母中能高水平表达。我们构建了一个酵母表达载体，通过克隆编码外源表位的盒式结构，能够快速产生不同的嵌合核心。FMDV核心和hCG核心都显示在颗粒表面呈现表位。酵母中产生的FMDV核心在一次低剂量免疫后能有效诱导豚鼠产生中和抗体。
