Victorian Infectious Diseases Reference Laboratory (VIDRL), Melbourne Health, The Peter Doherty Institute, Melbourne, Victoria 3000, Australia.
Royal Melbourne Institute of Technology (RMIT) University, School of Science, Melbourne, Victoria 3001, Australia.
Viruses. 2020 Jan 21;12(2):126. doi: 10.3390/v12020126.
Hepatitis B remains one of the major global health problems more than 40 years after the identification of human hepatitis B virus (HBV) as the causative agent. A critical turning point in combating this virus was the development of a preventative vaccine composed of the HBV surface (envelope) protein (HBsAg) to reduce the risk of new infections. The isolation of HBsAg sub-viral particles (SVPs) from the blood of asymptomatic HBV carriers as antigens for the first-generation vaccines, followed by the development of recombinant HBsAg SVPs produced in yeast as the antigenic components of the second-generation vaccines, represent landmark advancements in biotechnology and medicine. The ability of the HBsAg SVPs to accept and present foreign antigenic sequences provides the basis of a chimeric particulate delivery platform, and resulted in the development of a vaccine against malaria (RTS,S/AS01, Mosquirix), and various preclinical vaccine candidates to overcome infectious diseases for which there are no effective vaccines. Biomedical modifications of the HBsAg subunits allowed the identification of strategies to enhance the HBsAg SVP immunogenicity to build potent vaccines for preventative and possibly therapeutic applications. The review provides an overview of the formation and assembly of the HBsAg SVPs and highlights the utilization of the particles in key effective vaccines.
乙型肝炎仍然是全球主要的健康问题之一,自 40 多年前发现乙型肝炎病毒(HBV)是病原体以来,这种疾病一直存在。抗击这种病毒的一个关键转折点是开发了一种由乙型肝炎表面(包膜)蛋白(HBsAg)组成的预防性疫苗,以降低新感染的风险。从无症状 HBV 携带者的血液中分离出 HBsAg 亚病毒颗粒(SVPs)作为第一代疫苗的抗原,随后开发了在酵母中产生的重组 HBsAg SVPs 作为第二代疫苗的抗原成分,这代表了生物技术和医学的里程碑式进展。HBsAg SVPs 接受和呈现外来抗原序列的能力为嵌合颗粒递药平台提供了基础,并促成了疟疾疫苗(RTS,S/AS01,Mosquirix)的开发,以及针对尚无有效疫苗的传染病的各种临床前疫苗候选物。对 HBsAg 亚单位的生物医学修饰使得人们能够确定增强 HBsAg SVP 免疫原性的策略,从而构建用于预防和可能治疗用途的强效疫苗。本综述概述了 HBsAg SVPs 的形成和组装,并强调了这些颗粒在关键有效疫苗中的利用。