大肠杆菌表达的病毒样颗粒疫苗

重组病毒样颗粒是病毒衣壳蛋白外源表达的重要形式,形态结构与天然病毒高度相似,位于纳米尺度的大小易于被免疫系统识别,可激发机体产生保护性免疫反应,且不含有病毒基因,因此,是一种理想的疫苗形式,也是基于结构进行疫苗设计的重要结构载体。目前已上市的乙型肝炎疫苗、人乳头瘤病毒疫苗和戊型肝炎疫苗等基因工程疫苗均采用病毒样颗粒形式。大肠杆菌表达系统被广泛用于基因工程药物的生产,具有安全性好、生产周期短、易于放大生产等优点,在病毒样颗粒疫苗应用上具有良好前景。本文综述了利用大肠杆菌研制戊型肝炎疫苗和人乳头瘤病毒疫苗的进展,特别是这些病毒样颗粒疫苗的表达及组装、表位结构特征和临床试验结果。

Virus-like particle-based vaccine development using Escherichia coli expression system

Virus-like particles （VLPs） are generated by the self-assembly of viral structural protein using various expression systems. VLPs ensemble native virus particles in morphology and maintain key immune epitopes as authentic virus. In light of nanometer-sized particles with diameters of 20- 60 nm, VLPs were shown to be a passport to immune recognition, thus being capable of eliciting strong protective immune responses. Recombinant VLP-based vaccines have superior safety profiles due to lack of any viral genome. There are several licensed and highly successful VLP-based vaccines produced using recombinant DNAtechnology, such as recombinant hepatitis B, human papillomavirus and hepatitis E vaccine. E.coli expression system was well-established in production of biotherapeutics. This production platform for recombinant VLP-based vaccines has many advantages, such as rapid replication cycle and amenability for scale-up for commercial scale production. This review outlines the success of hepatitis E and human papillomavirus vaccines derived from E.coli. We highlight the protein expression, particle assembly, key epitope structure and clinical trials of these VLP-based vaccines.