治疗性乙型肝炎疫苗研究反思  

Introspection with Therapeutic Vaccine Researches on Chronic Hepatitis B

作　　者：陈国民[1,2] 

机构地区：[1]重庆医科大学生物医学工程学院 [2]重庆医科大学第一临床病学院感染性疾病教研组,重庆400016

出　　处：《科技导报》2013年第1期71-74,共4页Science & Technology Review

摘　　要："治疗性乙肝疫苗"是以乙肝病毒(HBV)的表面抗原(s抗原)为基础的生物制剂,目的是激发抗s抗原免疫反应,终止HBV慢性感染。HBV的e抗原与s抗原无抗原性关联,对e抗原的反应也与病毒及感染细胞的清除无关,因此以II期临床试验者血清有关病毒e抗原的数据结果,尚不能判断"治疗性乙肝疫苗"是否有效。疫苗的应用是抵御病毒入侵,而治疗性乙肝疫苗是在病毒已经进入人体后应用,在患者肝细胞可能广泛受累的情况下,疫苗一旦打破耐受激发抗s抗原免疫反应,除能清除血清中游离的病毒和s抗原颗粒外,将直接攻击被感染的肝细胞。由于无法估计慢性HBV感染者肝细胞感染程度,所以无法推测免疫反应发生后,免疫病理所致的肝损程度以及相应的风险。在应用上隐含如此风险,是"治疗性乙肝疫苗"走不出实验室的重要因素之一。To provoke an immune response against HBsAg in chronic HBV infections for interrupting the infection processes has been the purpose of therapeutic HBV vaccine. The vaccines research is basically the biological agents with the immunogenicity of HBV HBsAg. Due to the DNA sequence, the molecular structure and immunogenicity of HBsAg in HBV have no connection with those of HBV HbeAg at all; the HBeAg is a free and non-membrane antigen, therefore the anti-HBeAg response has no effect on the immune clearance reactions of HBV and infected hepatocytes in chronic HBV infections. Up to now, only with the clinical data about HBeAg system in serum with patients studied in Phase II clinical investigation, the treatment effectiveness of therapeutic HBV vaccine is still unable to be determined. The applications of vaccines is prophylactic in the sense of preventing viruses or bacteria from invasion, however the effort of therapeutic vaccines is that develops immune responses against persistent viral infections in an immune tolerant situation after exposure. It still remains a vision without the support from scientific rationale. Under the conditions of liver cells widespread infected by HBV in chronic HBV infection, while the anti-HBsAg response had been provoked with the treatment of therapeutic vaccine in these individuals, the free virus and HBsAg antigen particles in serum might be cleared, even the infected liver cells should be directly attacked as with accompanying circumstances, the degree of liver damage associated with the immune pathology as well as a corresponding risk could not possible estimate because of the infected degree of liver cells is hard to be estimated before chronic HBV infection treatment. Since the applications implicate such a risk, it is one of the important factors for the therapeutic HBV vaccine that is unable to get out of the laboratory. The future of therapeutic HBV vaccine seems doomed unless new and applicable immunologic principles are discovered.

关 键 词：慢性HBV感染 治疗性乙肝疫苗 免疫耐受 免疫病理 

分 类 号：R512.62[医药卫生—内科学]