In vivo administration of a lentiviral vaccine targets DCs and induces efficient CD8(+) T cell responses.
In vivo administration of a lentiviral vaccine targets DCs and induces efficient CD8(+) T cell responses.
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DOI：
10.1172/jci17098
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发表时间：
2003-06
期刊：
影响因子：
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通讯作者：
C. Esslinger;Laurence Chapatte;D. Finke;I. Miconnet;P. Guillaume;F. Lévy;H. Macdonald
中科院分区：
文献类型：
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作者：
C. Esslinger;Laurence Chapatte;D. Finke;I. Miconnet;P. Guillaume;F. Lévy;H. Macdonald
本研究评估了第三代慢病毒载体在体内施用T细胞疫苗方面的潜力。我们证明，lentivector注射到小鼠的足垫中转导出现在引流淋巴结和脾脏中的DC。此外，携带T细胞抗原的慢病毒载体疫苗在小鼠中诱导非常强的全身性抗原特异性细胞毒性T淋巴细胞（CTL）应答。在两种不同的抗原模型中进行的比较疫苗接种表明，在CTL应答的幅度和寿命方面，体内施用慢病毒载体上级转导的DC或肽/佐剂疫苗接种的转移。我们的数据表明，一个有效的T细胞启动慢病毒载体的决定性因素可能是靶向的DC原位和随后的迁移到次级淋巴器官。性能、易于应用和在人体中不存在预先存在的免疫力的组合使得基于慢病毒载体的疫苗成为癌症免疫疗法的有吸引力的候选者。
The present study evaluates the potential of third-generation lentivirus vectors with respect to their use as in vivo-administered T cell vaccines. We demonstrate that lentivector injection into the footpad of mice transduces DCs that appear in the draining lymph node and in the spleen. In addition, a lentivector vaccine bearing a T cell antigen induced very strong systemic antigen-specific cytotoxic T lymphocyte (CTL) responses in mice. Comparative vaccination performed in two different antigen models demonstrated that in vivo administration of lentivector was superior to transfer of transduced DCs or peptide/adjuvant vaccination in terms of both amplitude and longevity of the CTL response. Our data suggest that a decisive factor for efficient T cell priming by lentivector might be the targeting of DCs in situ and their subsequent migration to secondary lymphoid organs. The combination of performance, ease of application, and absence of pre-existing immunity in humans make lentivector-based vaccines an attractive candidate for cancer immunotherapy.