抗原-抗体复合物（HBsAg-antiHBsAg)治疗性乙肝疫苗随机对照试...

hantavirus

抗原-抗体复合物（HBsAg-antiHBsAg)治疗性乙肝疫苗随机对照试验(IIB)


A randomized controlled phase IIb trial of antigen-antibody immunogenic complex therapeutic vaccine in chronic hepatitis B patients.

Xu DZ, Zhao K, Guo LM, Chen XY, Wang HF, Zhang JM, Xie Q, Ren H, Wang WX, Li LJ, Xu M, Liu P, Niu JQ, Bai XF, Shen XL, Yuan ZH, Wang XY, Wen YM
Ditan Hospital, Beijing, China.

BACKGROUND: The safety of the immune complexes composed of yeast-derived hepatitis B surface antigen (HBsAg) and antibodies (abbreviated as YIC) among healthy adults and chronic hepatitis B patients has been proved in phase I and phase IIa trial. A larger number of patients for study of dosage and efficacy are therefore needed. METHODS AND PRINCIPAL FINDINGS: Two hundred forty two HBeAg-positive chronic hepatitis B patients were immunized with six injections of either 30 microg YIC, 60 microg of YIC or alum adjuvant as placebo at four-week intervals under code. HBV markers and HBV DNA were monitored during immunization and 24 weeks after the completion of immunization. The primary endpoint was defined as loss of HBeAg, or presence of anti-HBe antibody or suppression of HBV DNA, while the secondary endpoint was both HBeAg seroconversion and suppression of HBV DNA. Statistical significance was not reached in primary endpoints four weeks after the end of treatment among three groups, however, at the end of follow-up, HBeAg sero-conversion rate was 21.8%(17/78) and 9% (7/78) in the 60 microg YIC and placebo groups respectively (p = 0.03), with 95% confidence intervals at 1.5% to 24.1%. Using generalized estimating equations (GEEs) model, a significant difference of group effects was found between 60 microg YIC and the placebo groups in terms of the primary endpoint. Eleven serious adverse events occurred, which were 5.1%, 3.6%, and 5.0% in the placebo, 30 microg YIC and 60 microg YIC groups respectively (p>0.05). CONCLUSIONS: Though statistical differences in the preset primary and secondary endpoints among the three groups were not reached, a late and promising HBeAg seroconversion effect was shown in the 60 microg YIC immunized regimen. By increasing the number of patients and injections, the therapeutic efficacy of YIC in chronic hepatitis B patients will be further evaluated. TRIAL REGISTRATION: ChiCTR.org ChiCTR-TRC-00000022.


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“乙克”算是一个通过靶向DC提呈的机制来增强疫苗的免疫原性，具体原理是将HBsAg与Anti-HBsAg连接起来组成复合物，这时Anti-HBsAg抗体可以通过其Fc段与DC（体内主要抗原提呈细胞，可以激活初始T细胞)表面的Fc受体以及可能的DEC-205结合，把抗原带到DC表面，从而介导HBsAg内吞入DC等抗原提呈细胞。这样就可以提高机体对抗原的应答能力，从而达到增强疫苗免疫原性的目的。

ms001

乙克都有了，狂克呢？