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-7 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 addi-tion, this complex was used to immunize an HBsAg low-responder mouse strain (B10.S). Compared to the normal responsive counterpart mouse strain (BIO), immunization with HBsAg induced low titer of antibody, whereas, immunization using HBsAg-anti-HBs complex, BIO.S mice responded by producing similar level of anti-HBs as that induced in the BIO 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 recombinant HBsAg complexed to human high-titer anti-HBs immunoglobulin (HBIG) has been developed. Standard procedure for manufacturing this complex, as well as in vitro assay for monitoring its effect were also established. This complex will be further optimized for mass production and application for clinical trial will be submitted.