Polakos N K, Drane D, Cox J, Ng P, Selby M J, Chien D, O'Hagan D T, Houghton M, Paliard X
Chiron Corp., Emeryville, CA 94608, USA.
J Immunol. 2001 Mar 1;166(5):3589-98. doi: 10.4049/jimmunol.166.5.3589.
Current therapies for the treatment of hepatitis C virus (HCV) infection are only effective in a restricted number of patients. Cellular immune responses, particularly those mediated by CD8(+) CTLs, are thought to play a role in the control of infection and the response to antiviral therapies. Because the Core protein is the most conserved HCV protein among genotypes, we evaluated the ability of a Core prototype vaccine to prime cellular immune responses in rhesus macaques. Since there are serious concerns about using a genetic vaccine encoding for Core, this vaccine was a nonclassical ISCOM formulation in which the Core protein was adsorbed onto (not entrapped within) the ISCOMATRIX, resulting in approximately 1-microm particulates (as opposed to 40 nm for classical ISCOM formulations). We report that this Core-ISCOM prototype vaccine primed strong CD4(+) and CD8(+) T cell responses. Using intracellular staining for cytokines, we show that in immunized animals 0.30-0.71 and 0.32-2.21% of the circulating CD8(+) and CD4(+) T cells, respectively, were specific for naturally processed HCV Core peptides. Furthermore, this vaccine elicited a Th0-type response and induced a high titer of Abs against Core and long-lived cellular immune responses. Finally, we provide evidence that Core-ISCOM could serve as an adjuvant for the HCV envelope protein E1E2. Thus, these data provide evidence that Core-ISCOM is effective at inducing cellular and humoral immune responses in nonhuman primates.
目前用于治疗丙型肝炎病毒（HCV）感染的疗法仅对有限数量的患者有效。细胞免疫反应，尤其是由CD8(+)CTL介导的免疫反应，被认为在控制感染及对抗病毒疗法的反应中发挥作用。由于核心蛋白是各基因型中最保守的HCV蛋白，我们评估了一种核心原型疫苗在恒河猴中引发细胞免疫反应的能力。鉴于对使用编码核心蛋白的基因疫苗存在严重担忧，这种疫苗是一种非经典的免疫刺激复合物（ISCOM）制剂，其中核心蛋白吸附在（而非包埋于）ISCOMATRIX上，形成约1微米的微粒（与经典ISCOM制剂的40纳米相对）。我们报告称，这种核心-ISCOM原型疫苗引发了强烈的CD4(+)和CD8(+)T细胞反应。通过细胞内细胞因子染色，我们发现，在免疫动物中，循环CD8(+)和CD4(+)T细胞分别有0.30 - 0.71%和0.32 - 2.21%对天然加工的HCV核心肽具有特异性。此外，这种疫苗引发了Th0型反应，并诱导产生了高滴度的针对核心蛋白的抗体以及长期的细胞免疫反应。最后，我们提供证据表明核心-ISCOM可作为HCV包膜蛋白E1E2的佐剂。因此，这些数据证明核心-ISCOM在诱导非人类灵长类动物的细胞免疫和体液免疫反应方面是有效的。
