Strategies for designing vaccines eliciting Th1 responses in humans
Strategies for designing vaccines eliciting Th1 responses in humans
复制标题
DOI：
10.1016/s0168-1656(02)00131-1
复制
发表时间：
2002-09-25
影响因子：
4.1
通讯作者：
Moingeon, P
中科院分区：
文献类型：
--
作者：
Moingeon, P
目前主要的兴趣在于设计能够引发强细胞免疫应答的疫苗。细胞毒性和Th 1辅助细胞应答的诱导例如对于靶向慢性感染性疾病或癌症的疫苗（治疗性疫苗）是高度期望的。类似地，Th 1疫苗可用于重定向患有自身免疫性疾病和过敏症的患者中的不适当的抗原特异性免疫应答。重要的是，新兴技术和对免疫反应生理学的更好理解为合理设计此类疫苗提供了新的途径。基于鉴定和选择含有T细胞表位的免疫原的方法可以与表位增强策略一起使用，以增加与MHC的结合，或改善T细胞受体复合物的识别。优化的免疫原随后可以用适当的载体呈递给免疫系统，允许靶向专职抗原呈递细胞，如树突细胞。这样的抗原呈递平台可以单独使用或联合使用，作为混合免疫方案（异源初免-加强）的一部分，以引发广泛的免疫应答。Th 1佐剂的合理设计也可以受益于我们对促炎信号的性质的更好理解，这些促炎信号导致先天性和适应性免疫效应机制的启动。候选Th 1疫苗（或组分，如载体或佐剂）必须在探索性临床研究中进行测试，这意味着需要新的检测和方法，以定性和定量的方式评估人类低频T细胞应答。(C)2002 Elsevier Science B. V.保留所有权利。
There is currently a major interest in designing vaccines capable of eliciting strong cellular immune responses. The induction of cytotoxic and Th1 helper cellular responses is for example highly desirable for vaccines targeting either chronic infectious diseases or cancers (therapeutic vaccines). Similarly, Th1 vaccines would be useful in redirecting inappropriate antigen-specific immune responses in patients with autoimmune diseases and allergies. Importantly, emerging technologies and a better understanding of the physiology of immune responses offer new avenues to rationally design such vaccines. Approaches based on the identification and selection of immunogens containing T cell epitopes can be used, together with epitope-enhancement strategies, to increase binding to MHC, or to improve recognition by T cell receptor complexes. Optimized immunogens can subsequently be presented to the immune system with appropriate vectors allowing to target professional antigen-presenting cells, such as dendritic cells. Such antigen presentation platforms can be used alone or in association, as part of mixed immunization regimens (heterologous prime-boosts), in order to elicit broad immune responses. The rational design of Th1 adjuvants can also benefit from our better understanding of the nature of proinflammatory signals leading to the initiation of both innate and adaptive immune effector mechanisms. Candidate Th1 vaccines (or components such as vectors or adjuvants) will have to be tested in exploratory clinical studies, implying a need for new assays and methods allowing to assess in a qualitative and quantitative manner low-frequency T cell responses in humans. (C) 2002 Elsevier Science B.V. All rights reserved.