A totally synthetic vaccine of generic structure that targets Toll-like receptor 2 on dendritic cells and promotes antibody or cytotoxic T cell responses
A totally synthetic vaccine of generic structure that targets Toll-like receptor 2 on dendritic cells and promotes antibody or cytotoxic T cell responses
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DOI：
10.1073/pnas.0406740101
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发表时间：
2004-10-26
影响因子：
11.1
通讯作者：
Brown, LE
中科院分区：
文献类型：
--
作者：
Jackson, DC;Lau, YF;Brown, LE
描述了一种简单的通用肽基疫苗结构，其靶向表达toll样受体2的树突状细胞并引起其激活。疫苗是完全合成的，可作为佐剂，由(i)单个辅助性T细胞表位，（ii） CD8(+) T细胞或B细胞识别的靶表位，以及（iii）位于肽表位之间的靶向toll样受体2的脂质片段S-[2,3-二（棕榈酰氧基）丙基]半胱氨酸组成。检测的不同CD8(+) T细胞表位分别来自(i)流感病毒，（ii）细胞内单核增生李斯特菌，以及（iii）作为模型肿瘤抗原的卵清蛋白。含有来自胃泌素或促黄体生成素释放激素的B细胞表位作为B细胞表位的疫苗也被检查其引发抗体对抗母体激素的能力。每种疫苗都能够诱导CD8(+) T细胞或抗体介导的免疫反应。脂化疫苗，而非脂化疫苗，能够介导对病毒或细菌感染的保护，并介导预防和治疗性抗癌活性。这两种基于激素的疫苗诱导高抗体滴度，在黄体生成素释放激素的情况下导致生殖功能丧失。这些结果突出了简单的、完全合成的、基于表位的疫苗的实用性。
A simple generic peptide-based vaccine structure that targets Toll-like receptor 2-expressing dendritic cells and causes their activation is described. The vaccines are totally synthetic, serve as their own adjuvant, and are composed of (i) a single helper T cell epitope, (ii) a target epitope that is either recognized by CD8(+) T cells or B cells, and (iii) a Toll-like receptor 2-targeting lipid moiety, S-[2,3-bis(palmitoyloxy)propyl]cysteine, that is situated between the peptide epitopes to form a branched configuration. The different CD8(+) T cell epitopes examined were from (i) influenza virus, (ii) the intracellular bacterium Listeria monocytogenes, and (iii) ovalbumin as a model tumor antigen. Vaccines containing a B cell epitope from gastrin or luteinizing hormone-releasing hormone as a B cell epitope were also examined for their ability to elicit antibody against the parent hormones. Each of the vaccines was capable of inducing either CD8(+) T cell or antibody-mediated immune responses. The lipidated vaccines, but not the nonlipidated vaccines, were able to mediate protection against viral or bacterial infection and mediate prophylactic and therapeutic anticancer activity. The two hormone-based vaccines induced high antibody titers, which in the case of luteinizing hormone-releasing hormone resulted in abrogation of reproductive function. These results highlight the utility of simple, totally synthetic, epitope-based vaccines.