上海肝病在线 Shanghai Liver Diseases' Online

从病原间的Cross-talk中免疫佐剂样作用抑制病原复制而加重损伤再谈----治疗性复合HBV系列疫苗

众所周知，病原体作为异物而具有激活免疫系统作用，即免疫剌激/佐剂作用，免疫学上利用此一特性而作为诸多免疫低下病症如病毒感染和肿瘤的一重要治疗手段，如OK-432、BCG、胞必佳、高聚生、沙培林、多抗甲素、短小棒状杆菌菌苗 、 冻干麻疹活疫苗、卡介苗 及核酸多糖（PNS）、灵菌素、亮菌甲素等便是例证。同理，体内多种病原感染过过程中，因病原体间的相互作用（如病毒间的Viral cross-talk)致机体免疫系统激活，产生诸多抗病原物质和炎性介质，一方面对不同病原体有相互抑制作用，另一方面因加重机体损伤而机体病变加重。临床上不少慢乙肝病人合并其他病毒或病原感染后HBV复制暂时受抑，但病情加重而甚至重症化。因此如何利用病毒等病原间的相互作用（cross-talk）中病原体及成份的免疫佐剂特性来有效地激发机体的抗病原体免疫而又避免或少产生组织损伤是一有实际意义的研究课题。

近年的一报道应引导为重视，即利用大剂量无致病性鸟粘液囊病病毒的-attenuated variant (MTH-68/B)进行超感染，发现有治疗HBV和HCV肝损伤作用，因此今后的乙肝等病毒性肝损伤治疗中免疫佐剂应是有免疫促进活性，而没有明显的细胞毒性，即应是通过非胞溶性抗病毒机制而介导其生物学作秀的。我们正在设计中的治疗性复合HBV系列疫苗是采用多种微生物抗原作为免疫佐剂、其诱导的是一种非胞溶性（不损伤肝细胞）抗HBV免疫机制，其所引导发的HBV特异性免疫是强力、多位点、多克隆性的，因此可以说我们正在设计中的治疗性复合HBV系列疫苗是一有望根治HBV感染的治疗方法

Anticancer Res 1999 Jan-Feb;19(1B):629-33

Successful treatment of decompensated chronic viral hepatitis by bursal disease virus vaccine.

Csatary LK, Schnabel R, Bakacs T.

United Cancer Research Institute, Alexandria, VA, USA.

Three cases of women with chronic liver inflammation caused by hepatitis B (two) and C (one) viral infections, were followed up to twelve years after diagnosis. As conventional therapy was ineffective and the patients progressed into decompensated liver disease, they were superinfected with massive doses of an attenuated variant (MTH-68/B) of the apathogenic avian Bursal Disease virus (a double-stranded RNA virus from the Birnaviridae family). Clinical symptoms and biochemical abnormalities were resolved in two patients following few months of virus treatment. Cirrhosis was stabilized and significant clinical improvement was achieved in the third patient--who before the virus therapy was moribund with recurring, diuretic-resistant ascites, variceal bleedings, portal encephalopathy and renal failure. To our knowledge, these are the first recorded cases of decompensated chronic viral hepatitis which went to long-lasting remission or were stabilized by superinfection with an apathogenic virus.

PMID: 10216467 [PubMed - indexed for MEDLINE]