重组治疗性乙型肝炎疫苗(YIC)的实验研究  

Experimental Studies on Recombinant Hepatitis B Immunogenic Complex Therapeutic Vaccine (YIC)

作　　者：闻玉梅[1] 何丽芳[2] 瞿涤 马张妹 姚忻 

机构地区：[1]上海医科大学卫生部医学分子病毒重点实验室,上海200032 [2]上海医科大学卫生部医学分子病毒学重点实验室,上海200032

出　　处：《中国工程科学》1999年第1期38-42,共5页Strategic Study of CAE

基　　金：国家高技术研究发展计划;("863"计划)资助项目!(863-Z18-01)

摘　　要：研制了抗原－抗体复合物型乙肝治疗性疫苗。用小鼠实验证明这一治疗性疫苗的作用机理为：通过复合物中抗体Ｆｃ段与抗原呈递细胞表面的Ｆｃ受体结合，促进了细胞摄取抗原。复合物中的抗原经呈递后可比单纯抗原更有效地激活Ｔ细胞增殖，释放更多的γ－干扰素和白细胞介素－２，属ＴＨ１类型应答。复合物可在小鼠中诱生较单纯抗原诱生的抗－ＨＢｓ高１０倍以上。复合物还可诱生更强的细胞免疫，表现为经特异的抗原刺激后，γ－干扰素的 ｍＲＮＡ量增多。还发现复合物可在对 ＨＢｓＡｇ低应答鼠系中（Ｂ １０．Ｓ）诱生与正常应答鼠相当的抗体效价。在 ＨＢｓＡｇ阳性转基因鼠中，复合物可使部分鼠的 ＨＢｓＡｇ转为阴性，并可产生抗－ ＨＢｓ，反映这一疫苗具有疗效。为制备人用乙肝治疗性疫苗建立了用重组酵母菌表达的ＨＢｓＡｇ与人高效价抗乙肝免疫球蛋白组建治疗性疫苗的工艺，以及产品标化及效力的参比实验技术。A therapeutic vaccine composed of HBsAg complexed to anti-HBs (IC) has been developed for viral hepatitis B. Enhanced immune response was induced in hosts immunized with this complex, and the mechanisms of this vaccine was studied in mice. It was shown that the Fc fragment of anti-HBs in the complex was critical for induction of potent immune responses. The Fc fragment of the anti-HBs in the complex could attach to the Fc receptors on the antigen presenting cells (APC), increasing the uptake of HBsAg into these cells. After being ingested, the antigen complexed to antibody could be more effectively processed and presented to T cells. After incubation with macrophages previously treated with IC, T cells showed higher proliferation rate, and higher level of interferon-γ mRNA was detected. Enhanced immune response in host has also been shown by comparing anti-HBs titer in mice immunized with antigen-antibody complex versus the anti-HBs titer in mice immunized only with HBsAg. More than tenfold increase in anti-HBs was observed in the latter group. In addition, this complex was used to immunize an HBsAg low-responder mouse strain (B10. S). Compared to the normal responsive counterpart mouse strain (B10), immunization with HBsAg induced (cont. on. p. 57) (cont. from. p. 42) low titer of antibody, whereas, immunization using HBsAg-anti-HBs complex, B10.S mice responded by producing similar level of anti-HBs as that induced in the B10 mice. When the complex was used to immunize HBsAg positive transgenic mice (TgE), after four injections, in the female mice, 72% cleared HBsAg and developed anti-HBs (mean titer 1: 1070 by EIA); while in the male mice, 54% cleared HBsAg and developed anti-HBs (mean titer 1: 455 by EIA). Though some of non-immunized mice lost their HBsAg spontaneously during the experiment, none developed anti-HBs. Data showed that this immunogenic complex has promising potential to be used for the treatment of hepatitis B patients. For human use, a therapeutic vaccine composed of yeast-derived recombin

关 键 词：乙型肝炎 治疗性疫苗 抗原抗体复合物 免疫应答 

分 类 号：R512.62[医药卫生—内科学]