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Immunogenicity and safety of different injection routes and schedules of IC41, a Hepatitis C virus (HCV) peptide vaccine

机译:丙型肝炎病毒(HCV)肽疫苗IC41的不同注射途径和时间表的免疫原性和安全性

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Background: An effective vaccine would be a significant progress in the management of chronic HCV infections. This study was designed to examine whether different application schedules and injection routes may enhance the immunogenicity of the HCV peptide vaccine IC41.Methods: In this randomized trial 54 healthy subjects received either subcutaneous (s.c.) or intradermal (i.d.) vaccinations weekly (16 injections) or every other week (8 injections). One group additionally received imiquimod, an activator of the toll-like receptor (TLR) 7. The T cell epitope-specific immune response to IC41 was assessed using [H-3]-thymidine CD4+ T cell proliferation, interferon-gamma (IFN-gamma) CD8+ and CD4+ ELIspot and HLA-A*0201 fluorescence-activated cell sorting (FACS) tetramer-binding assays.Results: More than 60% of vaccinees responded in the CD4+ T cell proliferation assay in all groups. An HLA-A*0201 FACS tetramer-binding assay and IFN-gamma CD8+ ELIspot class I response of more than 70% was induced in four and three groups, respectively. IC41 induced significant immunological responses in all groups with responder rates of up to 100%. Interestingly, topical imiquimod was not able to enhance immunogenicity but was associated with a lower immune response. Local injection site reactions were mostly transient. Intradermal injections caused more pronounced reactions compared to s.c., especially erythema and edema.Conclusion: Compared to a previous study intensified dosing and/or i.d. injections enhanced the response rates to the vaccine IC41 in three assays measuring T cell function. Immunization with IC41 was generally safe in this study. These results justify testing IC41 in further clinical trials with HCV-infected individuals.
机译:背景:有效的疫苗将在控制慢性HCV感染方面取得重大进展。该研究旨在检查不同的应用时间表和注射途径是否可以增强HCV肽疫苗IC41的免疫原性。方法:在这项随机试验中,有54名健康受试者每周接受皮下(sc)或皮内(id)疫苗接种(16针)或每隔一周注射8次。一组还接受了咪喹莫特,后者是通行费样受体(TLR)7的激活剂。使用[H-3]-胸苷CD4 + T细胞增殖,干扰素-γ(IFN-γ)评估了对IC41的T细胞表位特异性免疫反应。 γ)CD8 +和CD4 + ELIspot以及HLA-A * 0201荧光激活细胞分选(FACS)四聚体结合测定法。结果:在所有组中,超过60%的疫苗在CD4 + T细胞增殖测定中有反应。在四组和三组中分别诱导出HLA-A * 0201 FACS四聚体结合测定和IFN-γCD8 + ELIspot I类应答超过70%。 IC41在所有组中均诱导了显着的免疫学应答,应答率高达100%。有趣的是,局部用咪喹莫特不能增强免疫原性,但与较低的免疫反应有关。局部注射部位反应大多是短暂的。与皮下注射相比,皮内注射引起更明显的反应,尤其是红斑和浮肿。结论:与先前的研究相比,加强了剂量和/或腹膜内注射。在三种测量T细胞功能的试验中,注射疫苗提高了对疫苗IC41的应答率。在这项研究中,使用IC41免疫通常是安全的。这些结果证明在进一步的HCV感染者临床试验中测试IC41是合理的。

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