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首页> 外文期刊>The Journal of biological chemistry >A Modular Approach to Assembly of Totally Synthetic Self-adjuvanting Lipopeptide-based Vaccines Allows Conformational Epitope Building
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A Modular Approach to Assembly of Totally Synthetic Self-adjuvanting Lipopeptide-based Vaccines Allows Conformational Epitope Building

机译：组装完全合成的自助脂肪脂肽的脂肽的疫苗组装模块化方法允许构象表位建设

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The technology described here allows the chemical synthesis of vaccines requiring correctly folded epitopes and that contain difficult or long peptide sequences. The final self-adjuvanting product promotes strong humoral and/or cell-mediated immunity. A module containing common components of the vaccine (T helper cell epitope and the adjuvanting lipid moiety S-[2,3-bis(palmitoyloxy)propyl]cysteine) was assembled to enable a plug and play approach to vaccine assembly. The inclusion within the module of a chemical group with chemical properties complementary and orthogonal to a chemical group present in the target epitope allowed chemoselective ligation of the two vaccine components. The heat-stable enterotoxin of enterotoxigenic Escherichia coli that requires strict conformational integrity for biological activity and the reproductive hormone luteinizing hormone-releasing hormone were used as the target epitopes for the antibody vaccines. An epitope from the acid polymerase of influenza virus was used to assemble a CD8+ T cell vaccine. Evaluation of each vaccine candidate in animals demonstrated the feasibility of the approach and that the type of immune response required, viz. antibody or cytotoxic T lymphocyte, dictates the nature of the chemical linkage between the module and target epitope. The use of a thioether bond between the module and target epitope had little or no adverse effect on antibody responses, whereas the use of a disulfide bond between the module and target epitope almost completely abrogated the antibody response. In contrast, better cytotoxic T lymphocyte responses were obtained when a disulfide bond was used.
机译：这里描述的技术允许需要正确折叠的表位并且含有困难或长肽序列的疫苗的化学合成。最终的自助助剂产品促进了强大的液体和/或细胞介导的免疫力。组装包含疫苗（T辅助单元表位和佐剂脂质部分S- [2,3-双（棕榈酰氧基）丙基]半胱氨酸）的模块，以使塞子和发挥疫苗组装的方法。将化学物质的模块内含物与化学性质互补和正交的化学性质与靶表位中存在的化学基团允许化学选择性连接两个疫苗组分。肠毒素大肠杆菌的热稳定肠毒素，需要对生物活性的严格构象完整性和生殖激素培养激素释放激素用作抗体疫苗的靶表位。来自流感病毒的酸聚合酶的表位用于组装CD8 + T细胞疫苗。对动物中每种疫苗候选者的评估证明了这种方法的可行性以及所需的免疫应答的类型viz。抗体或细胞毒性T淋巴细胞，决定了模块和靶表位之间的化学键的性质。在模块和靶表位之间使用硫醚键对抗体反应几乎没有不利影响，而使用模块与靶表位之间的二硫键几乎完全消除了抗体反应。相反，当使用二硫键时，获得了更好的细胞毒性T淋巴细胞反应。

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