Roohvand Farzin, Aghasadeghi Mohammad-Reza, Sadat Seyed Mehdi, Budkowska Agata, Khabiri Ali-Reza
Hepatitis and AIDS Department, Pasteur Institute of Iran, Pasteur Ave., Tehran 13164, Iran.
Biochem Biophys Res Commun. 2007 Mar 16;354(3):641-9. doi: 10.1016/j.bbrc.2006.12.232. Epub 2007 Jan 12.
An efficient vaccine against Hepatitis C virus (HCV) infection requires induction of strong humoral and cellular responses against viral proteins. We evaluated the immunogenicity of HCV core protein (HCVcp), a prime vaccine candidate, formulated in various human compatible adjuvants. An Escherichia coli-expressed HCVcp, purified in native conditions was used for murine immunization in separate groups of: free HCVcp (Ag), Ag+C/IFA (Freunds), Ag+CpG, Ag+M720 (Montanide ISA 720), Ag+F127 (Pluronic acid) and cocktails of Ag+F127+CpG and Ag+M720+CpG. Mice immunized with M720(+CpG) developed the highest HCVcp-specific titers of total IgG, IgG1, 2a, 2b, and that of IFN-gamma and IL-4 cytokines compared to all other groups. HCVcp-specific-CTLs against relevant MHC class I peptides were detected only for Ag+M720+CpG, Ag+M720, and Ag+CpG groups and could be blocked by antimouse-CD8 antibodies. While CTLs were stable, only F127 formulated groups demonstrated detectable IgG antibodies one year post-immunization. Hence, HCVcp formulated in M720 (with a synergistic effect by inclusion of CpG) could induce balanced and strong Th1/Th2 responses with long-lived CD4(-)CD8(+) CTLs.
一种有效的丙型肝炎病毒（HCV）感染疫苗需要诱导针对病毒蛋白的强烈体液免疫和细胞免疫反应。我们评估了HCV核心蛋白（HCVcp）作为主要疫苗候选物，在各种与人类兼容的佐剂中配制后的免疫原性。一种在大肠杆菌中表达、在天然条件下纯化的HCVcp被用于小鼠免疫，分为不同组：游离HCVcp（抗原）、抗原+C/IFA（弗氏佐剂）、抗原+CpG、抗原+M720（Montanide ISA 720）、抗原+F127（普朗尼克酸）以及抗原+F127+CpG和抗原+M720+CpG的混合物。与所有其他组相比，用M720（+CpG）免疫的小鼠产生了最高的HCVcp特异性总IgG、IgG1、2a、2b滴度，以及IFN-γ和IL-4细胞因子滴度。仅在抗原+M720+CpG、抗原+M720和抗原+CpG组中检测到针对相关MHC I类肽的HCVcp特异性CTL，并且可被抗小鼠-CD8抗体阻断。虽然CTL是稳定的，但仅F127配制组在免疫后一年表现出可检测到的IgG抗体。因此，在M720中配制的HCVcp（通过加入CpG具有协同作用）可诱导平衡且强烈的Th1/Th2反应以及具有长寿命的CD4（-）CD8（+）CTL。
