CPG 7909, an immunostimulatory TLR9 agonist oligodeoxynucleotide, as adjuvant to Engerix-B® HBV vaccine in healthy adults:: A double-blind phase I/II study
CPG 7909, an immunostimulatory TLR9 agonist oligodeoxynucleotide, as adjuvant to Engerix-B® HBV vaccine in healthy adults:: A double-blind phase I/II study
复制标题
DOI：
10.1007/s10875-004-6244-3
复制
发表时间：
2004-11-01
影响因子：
9.1
通讯作者：
Heathcote, J
中科院分区：
文献类型：
--
作者：
Cooper, CL;Davis, HL;Heathcote, J
在动物模型中，含有免疫刺激CpG基序（CpG ODN）的寡脱氧核苷酸作为一种强效的th1样免疫增强剂具有多种抗原。我们将这些观察结果扩展到CPG 7909添加到商业HBV疫苗中的安全性、耐受性和免疫原性的首次临床评估。在一项随机、双盲的I期剂量递增研究中，年龄在18-35岁的健康志愿者在0、4和24周时通过肌肉注射Engerix-B(R)（葛兰素史克公司）接种疫苗。将常规成人剂量的20杯重组乙型肝炎表面抗原（HBsAg）吸附在明矾上，与生理盐水（对照）或CPG 7909混合，以三种剂量（0.125、0.5或1.0 mg）中的一种给药。与对照组相比，CPG 7909接受者的hbsag特异性抗体反应（anti-HBs）在24周内的所有时间点出现得明显更快，而且明显更高（小于或等于0.001）。引人注目的是，大多数接种CpG 7909疫苗的受试者在接种启动疫苗后两周内就产生了具有保护作用的抗hbs IgG。与对照组相比，CPG 7909的两个高剂量组有更高的细胞毒性T细胞阳性反应率。最常见的不良反应是注射部位反应、流感样症状和头痛。而这些在CPG 7909组中比在对照组中更常见
Oligodeoxynucleotides containing immunostimulatory CpG motifs (CpG ODN) act as potent Th1-like immune enhancers with many antigens in animal models. We have extended these observations to the first clinical evaluation of the safety, tolerability and immunogenicity of CPG 7909 when added to a commercial HBV vaccine. In a randomized, double-blind phase I dose escalation study, healthy volunteers aged 18-35 years were vaccinated at 0, 4 and 24 weeks by intramuscular injection with Engerix-B(R) (GlaxoSmithKline). The regular adult dose of 20 mug recombinant hepatitis B surface antigen (HBsAg) adsorbed to alum was administered mixed with saline (control) or with CPG 7909 at one of three doses (0.125, 0.5 or 1.0 mg). HBsAg-specific antibody responses (anti-HBs) appeared significantly sooner and were significantly higher at all timepoints up to and including 24 weeks in CPG 7909 recipients compared to control subjects (pless than or equal to0.001). Strikingly, most CpG 7909-vaccinated subjects developed protective levels of anti-HBs IgG within just two weeks of the priming vaccine dose. A trend towards higher rates of positive cytotoxic T cell lymphocyte responses was noted in the two higher dose groups of CPG 7909 compared to controls. The most frequently reported adverse events were injection site reactions, flu-like symptoms and headache. While these were more frequent in CPG 7909 groups than in the control group (p