Department of Gastroenterology, Graduate School of Medicine, Kanazawa University, Kanazawa, Ishikawa, Japan.
PLoS One. 2018 Jun 1;13(6):e0198264. doi: 10.1371/journal.pone.0198264. eCollection 2018.
BACKGROUND & AIMS: Many individuals are infected with hepatitis B virus (HBV) worldwide, and this virus is commonly controlled by treatments with interferon (IFN)-alpha and nucleoside analogues (NA). However, the complete elimination of HBV by these treatments is difficult and, thus, the development of new treatments is needed. Host immune responses are closely involved in the elimination of HBV, suggesting the usefulness of immunotherapy. In the present study, we attempted to identify novel cytotoxic T-lymphocyte (CTL) epitopes that are useful for immunotherapy against HBV.
CTL epitopes were predicted using computer software. Immune responses to each peptide were evaluated by IFN-γ ELISPOT and cytotoxic assays. The relationships between the immune responses to these newly identified CTL epitopes and the clinical backgrounds of patients and administration of NA were analyzed. Peptides were administered to mice as vaccines and peptide-specific T-cell induction was measured in vivo.
Positive reactions to 10 synthesized peptides were detected in 3 or more patients using the IFN-γ ELISPOT assay, and concentration-dependent cytotoxicity against 2 of these peptides was observed in the cytotoxic assay. Some peptides that correlated with serum ALT, HBsAg, and HBV core-related antigen (HBcrAg) levels were identified. Immune reactions against some peptides were enhanced by the administration of NA. Regarding their effects as a vaccine, peptide-specific T-cells were induced by four peptides in vivo.
Novel HBV epitopes that correlated with HBsAg and HBcrAg levels were identified. These newly identified epitopes may be useful in the analysis of immune responses to HBV and development of immunotherapy against HBV.
全球许多人感染乙型肝炎病毒（HBV），这些病毒通常通过干扰素（IFN）-α和核苷类似物（NA）治疗来控制。然而，这些治疗方法很难完全消除 HBV，因此需要开发新的治疗方法。宿主免疫反应与 HBV 的消除密切相关，提示免疫疗法的有效性。本研究试图鉴定新的细胞毒性 T 淋巴细胞（CTL）表位，用于 HBV 的免疫治疗。
使用计算机软件预测 CTL 表位。通过 IFN-γ ELISPOT 和细胞毒性测定评估每种肽的免疫反应。分析这些新鉴定的 CTL 表位的免疫反应与患者的临床背景和 NA 治疗之间的关系。将肽作为疫苗给予小鼠，并在体内测量肽特异性 T 细胞诱导。
通过 IFN-γ ELISPOT 测定，在 3 名或更多患者中检测到 10 种合成肽的阳性反应，在细胞毒性测定中观察到对其中 2 种肽的浓度依赖性细胞毒性。鉴定出与血清 ALT、HBsAg 和 HBV 核心相关抗原（HBcrAg）水平相关的一些肽。NA 治疗增强了对某些肽的免疫反应。关于它们作为疫苗的效果，四种肽在体内诱导了肽特异性 T 细胞。
鉴定出与 HBsAg 和 HBcrAg 水平相关的新型 HBV 表位。这些新鉴定的表位可能有助于分析针对 HBV 的免疫反应和开发针对 HBV 的免疫疗法。
