A phase I study of the safety and immunogenicity of recombinant hepatitis B surface antigen co-administered with an immunostimulatory phosphorothioate oligonucleotide adjuvant
A phase I study of the safety and immunogenicity of recombinant hepatitis B surface antigen co-administered with an immunostimulatory phosphorothioate oligonucleotide adjuvant
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DOI：
10.1016/s0264-410x(03)00045-8
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发表时间：
2003-06-02
期刊：
影响因子：
5.5
通讯作者：
Eiden, JJ
中科院分区：
文献类型：
--
作者：
Halperin, SA;Van Nest, G;Eiden, JJ
某些带有CpG基序的寡聚脱氧核糖核酸可增强对联合递送抗原的免疫应答。我们进行了第一阶段，观察者盲法。在抗-HBs抗体阴性的健康成人中进行随机研究，探讨联合注射重组HBs Ag和免疫刺激DNA序列(ISS)10 18ISS的安全性和免疫原性。共设4个ISS剂量组(每组12个)：300、650、1000或3000杯。对于每组，两个对照组只接受20杯乙肝表面抗原，两个对照组只接受ISS，8名受试者接受ISS+20杯乙肝表面抗原。受试者每隔8周接受两次注射。注射部位反应(肢体运动压痛和疼痛)在ISS+HBs Ag剂量较高时更为常见，但主要是轻微的，持续时间较短。更高的抗-HBs抗体水平与更高的ISS剂量相关。第一次接种4周后，通过增加ISS剂量组(P<；0.05)，在第二次接种后1个月，分别有0.25%、75%和87.5%的受试者的血清保护性滴度(大于或等于10mIU/ml)增加到62.5、100、100和100%。增加ISS+HBs Ag剂量后，抗-HBs抗体几何平均水平在第一针后分别为1.2 2、5.78、2 4.75和206.5 mIU/ml，在第二针后分别为65.37、877.6、1 545和3 0 45mIU/ml。我们的结论是，在这一阶段的I期研究中，1018 ISS+HBs Ag在健康成年人中具有良好的耐受性和免疫原性，并可能在一剂或两剂后或在对标准疫苗方案无效的个人中提供增强乙肝病毒(HBV)免疫和保护的潜力。(C)2003爱思唯尔科学有限公司。保留所有权利。
Certain oligodeoxynuclotides with CpG motifs provide enhanced immune response to co-delivered antigens. We performed a phase 1, observer-blinded. randomized study in healthy anti-hepatitis B surface antigen (anti-HBsAg) antibody negative adults to explore safety and immunogenicity of co-injection of recombinant HBsAg combined with an immunostimulatory DNA sequence (ISS) 10 18 ISS. Four ISS dosage groups (N = 12 per group) were used: 300, 650, 1000 or 3000 mug. For each group, two controls received 20 mug HBsAg alone, two controls received ISS alone, and eight subjects received ISS + 20 mug HBsAg. Subjects received two doses 8 weeks apart. Injection site reactions (tenderness and pain on limb movement) were more frequent at higher ISS + HBsAg doses but were mainly mild and of short duration. Higher anti-HBsAa antibody levels were associated with higher ISS doses. Four weeks after the first dose, a seroprotective titer (greater than or equal to 10 mIU/ml) was noted for 0.25, 75, and 87.5% of subjects by increasing ISS dose group (P < 0.05) for those who received ISS +HBsAg; I month after the second dose this increased to 62.5, 100, 100, and 100%, respectively. Geometric mean anti-HBsAg antibody levels by increasing ISS + HBsAg dose were 1.22, 5.78, 24.75, and 206.5 mIU/ml after the first dose and 65.37, 877.6, 1545, and 3045 mIU/ml after the second dose. We conclude that 1018 ISS + HBsAg was well tolerated and immunogenic in this phase I study in healthy adults and may offer the potential for enhancement of hepatitis B virus (HBV) immunization and protection after one or two doses or in individuals who fail to respond to the standard vaccine regimen. (C) 2003 Elsevier Science Ltd. All rights reserved.