Immunogenicity and safety of a novel therapeutic hepatitis C virus (HCV) peptide vaccine: A randomized, placebo controlled trial for dose optimization in 128 healthy subjects
Immunogenicity and safety of a novel therapeutic hepatitis C virus (HCV) peptide vaccine: A randomized, placebo controlled trial for dose optimization in 128 healthy subjects
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DOI：
10.1016/j.vaccine.2006.03.009
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发表时间：
2006-05-15
期刊：
影响因子：
5.5
通讯作者：
Klade, Christoph S.
中科院分区：
文献类型：
--
作者：
Firbas, Christa;Jilma, Bernd;Klade, Christoph S.
由于以干扰素/利巴韦林为基础的标准疗法仅对大约一半的HCV患者有效，因此仍然需要寻找包括疫苗在内的替代疗法。新型肽疫苗IC41由5个含有HCV T细胞表位的合成肽和聚l -精氨酸作为合成佐剂组成。在这项随机、安慰剂对照试验中，128名HLA-A2阳性的健康志愿者每4周接种4种不同剂量的IC41、单独的HCV肽、单独的聚l -精氨酸或生理盐水。IC41是安全且耐受性良好的。轻度至中度的局部反应是短暂的。免疫原性通过T细胞表位特异性[H-3]胸苷增殖、ifn - γ ELIspot和hla -四聚体测定进行评估。各剂量组均有IC41诱导反应。在高剂量组中记录到较高的应答率，并且增加接种次数与较高的应答率和更强的应答相关。聚l-精氨酸是Th1/ tcl型免疫（分泌ifn - γ的T细胞）所必需的。(c) 2006 Elsevier Ltd.版权所有。
As interferon/ribavirin-based standard therapy is curative in only about half of HCV patients, there remains an important need for alternatives including vaccines. The novel peptide vaccine IC41 consists of five synthetic peptides harboring HCV T cell epitopes and poly-L-arginine as synthetic adjuvant. In this randomized, placebo-controlled trial, 128 HLA-A2 positive healthy volunteers received four s.c. vaccinations of seven different doses IC41, HCV peptides alone, p0ly-L-arginine alone or saline solution, every 4 weeks. IC41 was safe and well tolerated. Mild to moderate local reactions were transient. Immunogenicity was assessed using T cell epitope specific [H-3]-thymidine proliferation, IFN-gamma ELIspot and HLA-tetramer assays. IC41 induced responses in all dose groups. Higher responder rates were recorded in higher dose groups and increasing number of vaccinations were associated with higher responder rates and more robust responses. Poly-L-arginine was required for the aimed-for Th1/Tcl-type immunity (IFN-gamma secreting T cells). (c) 2006 Elsevier Ltd. All rights reserved.