乙型肝炎病毒抗原表位模拟多肽诱导CTL应答的研究

目的 应用分子设计技术设计治疗性多肽，以探讨基于乙型肝炎病毒(Hepatitis B virus，HBV)核心抗原优势细胞毒性T淋巴细胞(Cytotoxic T lymphocyts，CTL)表位的多肽设计与启动HLA-I限制性HBV特异性CD8^ T细胞应答的关系。方法 合成含HBcAg免疫优势CTL表位、Pre-S2蛋白优势B细胞表位和破伤风类毒素通用TH表位的多肽，并进行HLA-A2^ 人—PBMC体外和Balb／c小鼠体内免疫学功能研究。结果 上述多肽可在体内外诱导CD8^ CTL应答。以棕榈酸为分子内佐剂的Palm-p44可诱导较强的CD8^ CTL应答，与单纯多肽比较不需另加佐剂。结论 脂类分子内佐剂可显著提高多肽的免疫原性；Palm-p44可作为乙型肝炎治疗性多肽疫苗设计较有效的候选分子。

Therapeutic peptides based on HBcAg18-27 epitope can induce CTL response in vitro and in vivo

Objective To design by computerized molecular design methods therapeutic polypeptides against chronic hepatitis B infection to explore how to trigger HLA-Ⅰ restricted HBV specific CD8+ T cell response and hence eradicate viruses within hepatocytes.Methods A new panel of polypeptides comprised of the immunodominant CTL and B- epitopes of HBV core antigen(HBcAg) and Pre-S2 protein, and the tetanus toxoid T helper epitope were synthesized, and their immunological properties were investigated in HLA-A2+ human peripheral blood mononuclear cells(PBMCs)and in Balb/c mice. Results The results demonstrated that polypeptides consist of the three kinds of epitopes could evoke in human PBMCs and in mice CD8+ CTL response. Palm-p44, a polypeptide which covalently linked palmitic acids to the carboxyl-termini of the potent HBcAg CTL epitope as built-in adjuvant induced vigorous CD8+ CTL response, no additional adjuvants were necessary in comparison to the free CTL epitope which failed to induce cell mediated immunity in mice. Conclusions The findings indicate that the lipidic built-in adjuvant can efficiently improve the immunogenicity of peptide antigens, and Palm-p44 might be a promising candidate for therapeutic peptide vaccines against chronic viral hepatitis B infection.