Oseroff C, Sette A, Wentworth P, Celis E, Maewal A, Dahlberg C, Fikes J, Kubo R T, Chesnut R W, Grey H M, Alexander J
Epimmune, Incorporated, San Diego, CA 92121, USA.
Vaccine. 1998 May;16(8):823-33. doi: 10.1016/s0264-410x(97)00264-8.
Various peptide-based approaches to simultaneous induction of multiple cytotoxic T lymphocyte (CTL) responses were evaluated as part of ongoing efforts to develop immunotherapeutic vaccines for use in humans. To this end, HLA (human histocompatibility leukocyte antigen)-A2-restricted epitopes from several specific viral proteins were tested in an HLA-A2 transgenic mouse model system, which mimics human CTL responses to these viral proteins. Multiple CTL responses were elicited by immunization with either peptides emulsified in incomplete Freund's adjuvant (IFA), or lipidated peptides administered in phosphate buffered saline (PBS). In the case of lipidated peptides, induction of CTL responses was crucially dependent on the presence of helper T lymphocyte (HTL) epitopes, and most efficient in the case of lipidated covalently linked HTL-CTL epitope constructs. CTL could also be induced by immunization with lipidated HTL epitopes simply mixed with CTL epitopes and formulated in PBS. However, this approach was highly dependent on the particular lipidated HTL/CTL combination utilized, and was marginally effective for simultaneous priming of multiple CTL responses. By contrast, all HTL/CTL combinations were potent immunogens when delivered as lipidated, covalently linked molecules. This was the most effective of the approaches analysed in terms of multi-epitope priming, as demonstrated by the induction of simultaneous CTL responses to a pool of five different epitopes.
作为开发用于人类的免疫治疗疫苗的持续努力的一部分，评估了各种基于肽的方法来同时诱导多种细胞毒性T淋巴细胞（CTL）反应。为此，在HLA（人类组织相容性白细胞抗原）-A2转基因小鼠模型系统中测试了来自几种特定病毒蛋白的HLA-A2限制性表位，该系统模拟了人类对这些病毒蛋白的CTL反应。通过用不完全弗氏佐剂（IFA）乳化的肽或在磷酸盐缓冲盐水（PBS）中施用的脂肽进行免疫，引发了多种CTL反应。对于脂肽，CTL反应的诱导关键取决于辅助性T淋巴细胞（HTL）表位的存在，并且在脂化的共价连接的HTL-CTL表位构建体的情况下最有效。CTL也可以通过用简单地与CTL表位混合并在PBS中配制的脂化HTL表位进行免疫来诱导。然而，这种方法高度依赖于所使用的特定脂化HTL/CTL组合，并且对于同时启动多种CTL反应仅有微弱效果。相比之下，当作为脂化的共价连接分子递送时，所有HTL/CTL组合都是有效的免疫原。就多表位启动而言，这是所分析的方法中最有效的，如对一组五个不同表位同时诱导CTL反应所证明的那样。
