Roy P
Department of Biochemistry, University of Oxford, UK.
Intervirology. 1996;39(1-2):62-71. doi: 10.1159/000150476.
The Orbivirus genus within the family Reoviridae consists of nonenveloped architecturally complex viruses. The icosahedral viruses are 810 A diameter in size and are comprised of two protein shells containing seven proteins (VP1-VP7), surrounding a genome of ten double-stranded RNA segments. The prototype virus, bluetongue virus (BTV), is the etiological agent of a disease that can reach epidemic proportions among sheep and cattle. To develop highly protective virus-like particles, we have developed novel baculovirus multigene expression vector systems which have allowed us to coexpress three, four or five BTV genes from single recombinant vectors. The resultant particulate structures resemble BTV virus-like and subvirus-like particles which are structurally and immunologically indistinguishable from the BTV, and preliminary clinical trials have verified this vaccines safety and efficacy. Unlike live virus vaccines, VLPs are noninfectious and lack virus (or other) DNA/RNA required for replication. VLPs do not replicate in host cells. However, sheep trials have shown that VLPs are more immunogenic than subunit vaccines (viral proteins), or viruses killed by chemical inactivation. In addition, they are effective at eliciting humoral, cell-mediated and mucosal immunities. Virus-like particles (VLPs) are safe to produce and handle. The baculovirus vector and host cells used to make VLPs do not come from mammalian sources (hence they do not contain mammalian-derived pathogens). The multicomponent VLPs have also been utilized as vaccine delivery systems for multiple immunogens including B and T cell epitopes. The expression system described here is a tool which may have a range of applications in industries employing biotechnology to produce vaccines, insecticides, diagnostic and protein reagents.
呼肠孤病毒科的环状病毒属由无包膜、结构复杂的病毒组成。这些二十面体病毒直径为810埃，由两个包含七种蛋白质（VP1-VP7）的蛋白壳组成，围绕着一个由十个双链RNA片段组成的基因组。原型病毒蓝舌病毒（BTV）是一种可在绵羊和牛群中引发流行疾病的病原体。为了开发具有高度保护性的病毒样颗粒，我们开发了新型杆状病毒多基因表达载体系统，该系统使我们能够从单个重组载体中共表达三个、四个或五个BTV基因。所产生的颗粒结构类似于BTV病毒样颗粒和亚病毒样颗粒，在结构和免疫学上与BTV无法区分，初步临床试验已证实了这种疫苗的安全性和有效性。与活病毒疫苗不同，病毒样颗粒无感染性，缺乏复制所需的病毒（或其他）DNA/RNA。病毒样颗粒不在宿主细胞中复制。然而，绵羊试验表明，病毒样颗粒比亚单位疫苗（病毒蛋白）或化学灭活的病毒更具免疫原性。此外，它们在引发体液免疫、细胞介导免疫和粘膜免疫方面有效。病毒样颗粒（VLPs）生产和处理安全。用于制造病毒样颗粒的杆状病毒载体和宿主细胞并非来自哺乳动物来源（因此它们不含有哺乳动物源性病原体）。多组分病毒样颗粒也已被用作多种免疫原的疫苗递送系统，包括B细胞和T细胞表位。这里描述的表达系统是一种工具，可能在利用生物技术生产疫苗、杀虫剂、诊断试剂和蛋白质试剂的行业中有一系列应用。
