Pharmaceutical Research Laboratories, Toray Industries, Inc, Kanagawa, Japan.
Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan.
Gut. 2018 Feb;67(2):372-379. doi: 10.1136/gutjnl-2016-312208. Epub 2016 Oct 26.
Although HCV is a major cause of chronic liver disease worldwide, there is currently no prophylactic vaccine for this virus. Thus, the development of an HCV vaccine that can induce both humoural and cellular immunity is urgently needed. To create an effective HCV vaccine, we evaluated neutralising antibody induction and cellular immune responses following the immunisation of a non-human primate model with cell culture-generated HCV (HCVcc).
To accomplish this, 10 common marmosets were immunised with purified, inactivated HCVcc in combination with two different adjuvants: the classically used aluminum hydroxide (Alum) and the recently established adjuvant: CpG oligodeoxynucleotide (ODN) wrapped by schizophyllan (K3-SPG).
The coadministration of HCVcc with K3-SPG efficiently induced immune responses against HCV, as demonstrated by the production of antibodies with specific neutralising activity against chimaeric HCVcc with structural proteins from multiple HCV genotypes (1a, 1b, 2a and 3a). The induction of cellular immunity was also demonstrated by the production of interferon-γ mRNA in spleen cells following stimulation with the HCV core protein. These changes were not observed following immunisation with HCVcc/Alum preparation. No vaccination-related abnormalities were detected in any of the immunised animals.
The current preclinical study demonstrated that a vaccine included both HCVcc and K3-SPG induced humoural and cellular immunity in marmosets. Vaccination with this combination resulted in the production of antibodies exhibiting cross-neutralising activity against multiple HCV genotypes. Based on these findings, the vaccine created in this study represents a promising, potent and safe prophylactic option against HCV.
虽然 HCV 是全球慢性肝病的主要病因，但目前尚无针对该病毒的预防性疫苗。因此，迫切需要开发一种能够诱导体液和细胞免疫的 HCV 疫苗。为了研制有效的 HCV 疫苗，我们评估了用细胞培养产生的 HCV（HCVcc）免疫非人灵长类动物模型后诱导中和抗体和细胞免疫应答的情况。
为了实现这一目标，用纯化的灭活 HCVcc 联合两种不同佐剂（经典的氢氧化铝佐剂（Alum）和最近建立的佐剂：被裂褶多糖（K3-SPG）包裹的 CpG 寡脱氧核苷酸（ODN））对 10 只普通狨猴进行免疫。
HCVcc 与 K3-SPG 联合给药能有效诱导针对 HCV 的免疫应答，这表现为针对来自多种 HCV 基因型（1a、1b、2a 和 3a）的嵌合 HCVcc 结构蛋白产生具有特异性中和活性的抗体。HCV 核心蛋白刺激脾细胞产生干扰素-γ mRNA 也证明了细胞免疫的诱导。用 HCVcc/Alum 制剂免疫后未观察到这些变化。在任何免疫的动物中均未检测到与疫苗接种相关的异常。
本临床前研究表明，含有 HCVcc 和 K3-SPG 的疫苗能在狨猴中诱导体液和细胞免疫。用这种组合进行免疫可产生针对多种 HCV 基因型具有交叉中和活性的抗体。基于这些发现，本研究中所构建的疫苗是一种有前途的、有效和安全的 HCV 预防性选择。
