IN SITU GENE-MODIFIED DCS FOR AN HIV-1 T CELL VACCINE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 尽管已经制定了针对许多病毒性传染病的保护性疫苗接种策略，但20年来，针对艾滋病毒-1的广泛活性的疫苗一直难以找到。细胞免疫涉及(1)调节HIV-1复制，(2)延缓疾病进展，以及(3)预防感染，认为它们是成功免疫战略的重要组成部分。树突状细胞(DC)可通过MHC-I、II类途径递呈抗原，在细胞免疫应答中发挥重要作用。因此，基于DC的疫苗目前正被开发为诱导强烈的抗原特异性T细胞反应的试剂，但这些方案通常需要对DC进行体外基因修饰，然后重新输注回自体或MHC匹配的宿主，在那里它们成熟，迁移到淋巴结，并将候选抗原呈现给CD4和/或CD8T细胞以引发抗原特异性反应。虽然体外基因操作方法在建立实验环境中的概念验证方面是有用的，但开发用于该领域的预防性疫苗是不现实的。如果DC的转导能够在原位完成，DC靶向疫苗作为预防性药物的广泛使用将更加可行。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Although protective vaccination strategies have been developed against many infectious diseases of viral origin, a vaccine with broad activity against HIV-1 has remained elusive for two decades. Cell-mediated immunity has been implicated in (i) modulation of HIV-1 replication, (ii) protraction of disease progression, and (iii) protection against infection, arguing their importance as components of a successful immunization strategy. Dendritic cells (DC) can present antigens via MHC class I and II pathways and are central to the development of cell-mediated immune responses. Thus, DC-based vaccines are currently being developed as agents to elicit strong, antigen-specific T cell responses, but these protocols usually require ex vivo genetic modification of DCs, followed by re-infusion back into an autologous or MHC-matched host where they mature, migrate to lymph nodes, and present the candidate antigen to CD4 and/or CD8 T cells to elicit antigen-specific responses. Although the ex vivo genetic manipulation approach has been useful in establishing proof-of-concept in an experimental setting, it is not practical for the development of prophylactic vaccines to be used in the field. If transduction of the DCs could be accomplished in situ, the broad use of DC-targeted vaccines as prophylactic agents would be more feasible.