APASL2013 胸腺肽α1抗HBV-DC疫苗联合HBeAg阴性临床试验

StephenW

A Clinical Trial on Anti-HBV-DC Vaccine Combined with Thymosin-α1 in the HBeAg Negative Chronic Hepatitis B Patients

Bang-Fu Wu1,2, Jiang-Ying Yang2, Ya-Lin Zhang3, Yong Liu1, Hui-Hua Zhou3, Xuan-Qin Wang1, Fang-Qin Li1, Chun-Qiong Hou3, Xue-Song Li1, Xiang-Hua Huang1, Zheng-Sheng Xiao1, Ming Yang1, Fu-Xin Lin3, Wei Chen3, Yan-Ping Fu3, Shuo Zheng3, Yun Zhou2, Jun Yang2, Xin-He Wan1, Hui Huang1
1Gastroenterology and Hepatology Center, Southern Medical University Renkang Hospital, Dongguan, 2Guangzhou Pubang Bio-Immunological Tech Research Institute, Guangzhou, 3Gastroenterology and Hepatology Center, Tongji Medical College Affiliated Dongguan Hospital, Huazhong University of Science and Technology, Dongguan, China

Background/aims: To observe the clinical efficacy of anti-HBV-DC vaccine, the dendritic cells originating from peripheral blood mononuclear cells(PBMC) sensitized by HBsAg, in combination with thymosin-α1, in the HBeAg negative chronic hepatitis B(CHB) patients.
Methods: 25 patients were recruited in the trial including 18 with ALT≤2ULN and 7 with ALT>2ULN. PBMCs obtained from 50ml of heparinized peripheral blood through density gradient centrifuge and adherence method were proliferated under the induction by GM-CSF and IL-4, and sensitized with the stock of hepatitis B vaccine containing 30µg HBsAg on day 5 and with hepatitis B vaccine commercially available containing 20µg HBsAg on day 6. anti-HBV-DC vaccine was harvested on day 7 and injected, half hypodermically and half intravenously, to the patient once every two weeks for 12 practices applications totally. Thymosin-α1 1.6mg was injected hypodermically twice a week. Quantitative HBVM(TRFIA) and HBVDNA and hepatic functions were evaluated at week 0, 4, 12, and 24.
Results: Mean of HBsAg, ATL and TBIL decreased gradually along the time from week 4, 12 to 24, with significant difference compared with the values prior to treatment. At week 4, 12 and 24, HBsAg negative conversion rate were 8.00%(2/25), 12.00(3/25) and 20.00%(5/25) respectively, HBVDNA negative conversion rate were 63.64%(7/11), 72.73%(8/11) and 72.73%(8/11), ALT normalization rate were 48.00%(12/25), 64.00%(16/25) and 80.00%(20/25), and HBsAg negative conversion rate was 11.11%(2/18), 16.67%(3/18) and 22.22%(4/18) in patients with ALT≤2ULN. But HBsAg negative conversion occurred only in one patient (14.29%, 1/7) those with ALT>2ULN at week 24. The rate of adverse effect was 2.67% observed in reinfusion of anti-HBV-DC vaccine.
Conclusions: anti-HBV-DC vaccine in combination with thymosin-α1 can be considered as a safe approach with high efficacy for HBeAg negative CHB patients, which can effectively inhibit the viral replication, decrease rapidly and eliminate the HBsAg and HBVDNA from body.


Assigned speakers:
Dr. Jiang-Ying Yang, Guangzhou Pubang Bio-Immunological Tech Research Institute , Guangzhou , China

Assigned in sessions:
07.06.2013, 08:30-17:30, PT-4, HEP B Clinical, Exhibition Hall

StephenW

背景/目的：观察抗HBV-DC疫苗的临床疗效，从外周血单个核细胞（PBMC），乙肝表面抗原致敏的树突状细胞，在用胸腺肽α1相结合，在HBeAg阴性慢性乙型肝炎（CHB）的患者。
方法：25例患者在试用招募，其中包括18名与ALT≤2ULN和7 ALT> 2ULN。 GM-CSF和IL-4的诱导下获得通过密度梯度离心和贴壁法从50ml肝素外周血中的单核细胞增生，致敏股票乙肝疫苗的第5天含30μg的乙肝表面抗原和乙肝疫苗商业第6天含20μg乙肝表面抗原。抗HBV-DC疫苗是在第7天收获，皮下的一半，另一半静脉内注入12实践应用类型的​​病人每两周一次。胸腺素α11.6mg皮下注射，每周两次。定量乙肝病毒标志物（TRFIA）和HBVDNA和肝功能评估在第0周，4，12，和24。
结果：平均乙肝表面抗原，ATL和TBIL沿着时间逐渐下降，从第4周，12〜24，与治疗前的值相比有显着差异。在第4周，12和24，乙肝表面抗原转阴率分别为8.00％（2/25），12.00（3/25）和20.00％（5/25），HBVDNA阴转率分别为63.64％（7/11）， 72.73％（8/11）和72.73％（8/11），ALT复常率分别为48.00％（12/25），64.00％（16/25）和80.00％（20/25），HBsAg的阴转率为11.11％（2/18），16.67％（3/18）和22.22％（4/18）的患者ALT≤2ULN。但是，乙肝表面抗原转阴只发生在一个病人（14.29％，1/7），24周时ALT> 2ULN。不利影响的速率是2.67％中观察到的抗HBV-DC疫苗回输。
结论：结合胸腺肽α1抗HBV-DC疫苗可以被视为一种安全的方法，疗效高HBeAg阴性慢性乙型肝炎患者，可有效抑制病毒复制，快速降低和消除HBsAg和HBVDNA从身体。