Attempted therapeutic immunization in a chimpanzee chronic HBV carrier with a high viral load.
Attempted therapeutic immunization in a chimpanzee chronic HBV carrier with a high viral load.
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尝试对高病毒载量的黑猩猩慢性乙型肝炎病毒携带者进行治疗性免疫。
DOI：
10.1111/j.1600-0684.2006.00152.x
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发表时间：
2006
影响因子：
0.7
通讯作者：
Prince,AlfredM
中科院分区：
文献类型：
--
作者：
Shata,MohamedTarekM;Pfahler,Wolfram;Brotman,Betsy;Lee,Dong-Hun;Tricoche,Nancy;Murthy,Krishna;Prince,AlfredM
背景我们先前报道了在具有相对低病毒载量的黑猩猩中成功的治疗性免疫，其用重组质粒B肝炎表面抗原（HBsAg）DNA免疫并用编码金丝雀痘病毒的重组HBsAg加强免疫。在本研究中，我们试图证实这些发现在动物中具有高病毒load.Methods和ResultsWe测试了三个免疫策略连续超过3年的时间。在第一项研究中，我们每月注射4次编码HBsAg + PreS 2+肝炎B核心抗原（HBcAg）+编码白细胞介素（IL）-12的DNA（3天后注射），并在首次免疫后6个月用表达所有上述HBV基因的金丝雀痘加强免疫。 未观察到病毒载量降低。在第二个试验中，我们给予拉米夫定8周，然后开始每月用表达上述病毒基因的质粒进行DNA免疫;然而，拉米夫定治疗终止后1周病毒载量反弹。 在第三个试验中，我们继续拉米夫定治疗30周，并在拉米夫定治疗开始后18周和23周用表达上述病毒基因的牛痘病毒免疫。 拉米夫定治疗停止后不久病毒载量再次反弹。对细胞介导的免疫应答及其亲合力的分析显示，基于DNA的免疫产生了高亲合力T细胞应答的最强增强，而拉米夫定治疗期间的重组牛痘免疫仅增强了低亲合力应答。最强的低和高的亲和力反应是针对中间的表面antigen.ConclusionsThree策略治疗性免疫未能控制HBV病毒血症在慢性感染的黑猩猩与高病毒载量。
BackgroundWe previously reported successful therapeutic immunization in a chimpanzee having a relatively low viral load, which was immunized with recombinant plasmid hepatitis B surface antigen (HBsAg) DNA and boosted with recombinant HBsAg encoding canarypox virus. In the present study, we attempted to confirm these findings in an animal with a high virus load.Methods and ResultsWe tested three immunization strategies successively over a 3‐year period. In the first of these, we administered four monthly injections of DNA encoding HBsAg + PreS2 + hepatitis B core antigen (HBcAg) + DNA encoding interleukin (IL)‐12, (given 3 days later), and boosted with canarypox expressing all of the above HBV genes 6 months after initial immunization. No reduction in viral load was observed. In the second trial, we administered lamivudine for 8 weeks, and then began monthly DNA‐based immunization with plasmids expressing the above viral genes; however, viral loads rebounded 1 week after termination of lamivudine therapy. In a third trial, we continued lamivudine therapy for 30 weeks and immunized with vaccinia virus expressing the above viral genes 18 and 23 weeks after the start of lamivudine therapy. Again viral loads rebounded shortly after cessation of lamivudine treatment. Analysis of cell‐mediated immune responses, and their avidity, revealed that DNA‐based immunization produced the strongest enhancement of high avidity T‐cell responses, while recombinant vaccinia immunization during lamivudine therapy enhanced low avidity responses only. The strongest low and high avidity responses were directed to the middle surface antigen.ConclusionsThree strategies for therapeutic immunization failed to control HBV viremia in a chronically infected chimpanzee with a high viral load.