Partially randomized, non-blinded trial of DNA and MVA therapeutic vaccines based on hepatitis B virus surface protein for chronic HBV infection.
Partially randomized, non-blinded trial of DNA and MVA therapeutic vaccines based on hepatitis B virus surface protein for chronic HBV infection.
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DOI：
10.1371/journal.pone.0014626
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发表时间：
2011-02-15
期刊：
影响因子：
3.7
通讯作者：
McConkey SJ
中科院分区：
文献类型：
--
作者：
Cavenaugh JS;Awi D;Mendy M;Hill AV;Whittle H;McConkey SJ
慢性HBV感染3.5亿人，导致癌症和肝功能衰竭。我们的目的是评估质粒DNA（pSG2.HBs）疫苗的安全性和有效性，其次是重组修饰的安卡拉痘苗病毒（MVA. HBs），编码HBV表面抗原作为治疗慢性HBV。第二个目标是表征免疫应答。首先，32名HBV e抗原阴性（eAg-）参与者被随机分配到四组之一：单独接受疫苗，单独接受拉米夫定（3TC），两者兼而有之，或都不接受。随后，两组中的16名eAg+志愿者接受单独的3TC或3TC和疫苗。最后，12例eAg-和12例eAg+受试者入组较高剂量治疗组。居住在冈比亚西部的15 - 25岁的健康但慢性HBV感染的男性符合条件。某些组的受试者接受1 mg或2 mg pSG2.HBs肌内注射两次，随后每3周皮内注射5 × 107 pfu或1.5 × 108 pfu MVA. HBs，伴或不伴3TC，持续11 - 14周。阴性对照组皮内接种狂犬病疫苗。安全性进行了临床和生化评估。疗效的主要指标是血浆HBV的定量PCR检测。通过IFN-γ ELISpot和细胞内细胞因子染色评估免疫力。接种疫苗后观察到轻度局部和全身不良事件。在一些病例中，在MVA.重建后观察到小的闪亮疤痕。AST或ALT无明显变化。高剂量组中有一名参与者的HBeAg丢失。正如预期，3TC治疗降低了治疗期间的病毒血症水平，但初免-加强疫苗方案并未降低病毒血症。免疫反应是可变的。IFN-γ主要由抗原非特异性CD16+细胞（CD3+和CD3-）产生。疫苗耐受性良好，但不能控制HBV感染。ISRCTN ISRCTN 67270384
Chronic HBV infects 350 million people causing cancer and liver failure. We aimed to assess the safety and efficacy of plasmid DNA (pSG2.HBs) vaccine, followed by recombinant modified vaccinia virus Ankara (MVA.HBs), encoding the surface antigen of HBV as therapy for chronic HBV. A secondary goal was to characterize the immune responses. Firstly 32 HBV e antigen negative (eAg–) participants were randomly assigned to one of four groups: to receive vaccines alone, lamivudine (3TC) alone, both, or neither. Later 16 eAg+ volunteers in two groups received either 3TC alone or both 3TC and vaccines. Finally, 12 eAg– and 12 eAg+ subjects were enrolled into higher-dose treatment groups. Healthy but chronically HBV-infected males between the ages of 15 – 25 who lived in the western part of The Gambia were eligible. Participants in some groups received 1 mg or 2 mg of pSG2.HBs intramuscularly twice followed by 5×107 pfu or 1.5×108 pfu of MVA.HBs intradermally at 3-weekly intervals with or without concomitant 3TC for 11–14 weeks. Intradermal rabies vaccine was administered to a negative control group. Safety was assessed clinically and biochemically. The primary measure of efficacy was a quantitative PCR assay of plasma HBV. Immunity was assessed by IFN-γ ELISpot and intracellular cytokine staining. Mild local and systemic adverse events were observed following the vaccines. A small shiny scar was observed in some cases after MVA.HBs. There were no significant changes in AST or ALT. HBeAg was lost in one participant in the higher-dose group. As expected, the 3TC therapy reduced viraemia levels during therapy, but the prime-boost vaccine regimen did not reduce the viraemia. The immune responses were variable. The majority of IFN-γ was made by antigen non-specific CD16+ cells (both CD3+ and CD3–). The vaccines were well tolerated but did not control HBV infection. ISRCTN ISRCTN67270384
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影响因子：
5.4
作者：
Depla, Erik;Van der Aa, Annegret;Meheus, Lydie
通讯作者：
Meheus, Lydie
影响因子：
3.4
作者：
Cavenaugh, James S.;Snell, Paul;McConkey, Samuel J.
通讯作者：
McConkey, Samuel J.
DOI：
10.1073/pnas.88.23.10445
发表时间：
1991-12-01
影响因子：
11.1
作者：
BERTOLETTI, A;FERRARI, C;CHISARI, FV
通讯作者：
CHISARI, FV
影响因子：
3.7
作者：
Gilbert, SC;Schneider, J;Hill, AVS
通讯作者：
Hill, AVS
影响因子：
20.3
作者：
Fehniger, TA;Cooper, MA;Caligiuri, MA
通讯作者：
Caligiuri, MA