Abrignani S, Rosa D
IRIS Research Centre, Chiron S.p.A., Siena, Italy.
Clin Diagn Virol. 1998 Jul 15;10(2-3):181-5. doi: 10.1016/s0928-0197(98)00028-2.
Natural hepatitis C virus (HCV) infection elicits poor immunity. Although HCV proteins elicit immune responses in virtually all cases of infection, the great majority of HCV infections become chronic. Currently, no vaccine is available for HCV despite an estimated incidence of approximately 50000 new cases per year in the USA alone.
To discuss how the problems associated with developing a vaccine against HCV infection may be overcome and describe recent progress made towards overcoming these problems and developing a vaccine.
A cytofluorimetric assay that can assess the ability of a serum sample to neutralise the binding of the HCV-envelope glycoprotein E2 to human cells (neutralisation of binding or NOB assay) was developed. The assay was used to assess the levels of antibodies capable of neutralising E2 binding in the sera of vaccinated and carrier chimpanzees.
Low titres of NOB antibodies were found in the majority of chimpanzees challenged with HCV infection. Chimpanzees immunised with the E1/E2 heterodimer developed NOB antibodies and high levels of neutralising antibodies. These chimpanzees were not protected from challenge with heterologous virus but were protected from subsequent chronic infection.
A subunit vaccine composed of recombinant HCV proteins may protect from infection or chronic infection by different HCV genotypes.
自然感染丙型肝炎病毒(HCV)会引发较差的免疫反应。尽管HCV蛋白在几乎所有感染病例中都会引发免疫反应,但绝大多数HCV感染都会发展为慢性感染。目前,尽管仅在美国每年估计就有大约50000例新发病例,但仍没有针对HCV的疫苗。
讨论如何克服与研发抗HCV感染疫苗相关的问题,并描述在克服这些问题及研发疫苗方面取得的最新进展。
开发了一种细胞荧光分析方法,该方法可以评估血清样本中和HCV包膜糖蛋白E2与人细胞结合的能力(结合中和或NOB分析)。该分析方法用于评估接种疫苗的黑猩猩和携带病毒的黑猩猩血清中能够中和E2结合的抗体水平。
在大多数受到HCV感染攻击的黑猩猩中发现了低滴度的NOB抗体。用E1/E2异二聚体免疫的黑猩猩产生了NOB抗体和高水平的中和抗体。这些黑猩猩没有受到异源病毒攻击的保护,但受到了后续慢性感染的保护。
由重组HCV蛋白组成的亚单位疫苗可能会预防不同HCV基因型的感染或慢性感染。