Directly injected lentiviral vector-based T cell vaccine protects mice against acute and chronic viral infection.
Directly injected lentiviral vector-based T cell vaccine protects mice against acute and chronic viral infection.
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DOI：
10.1172/jci.insight.161598
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发表时间：
2022-09-22
期刊：
影响因子：
8
通讯作者：
Landau, Nathaniel R.
中科院分区：
文献类型：
--
作者：
Tada, Takuya;Norton, Thomas D.;Leibowitz, Rebecca;Landau, Nathaniel R.
基于慢病毒载体的树突状细胞疫苗在动物模型中诱导针对病毒感染和癌症的保护性T细胞应答。在这项研究中，我们测试了是否可以通过直接注射抗原表达慢病毒载体来实现预防性和治疗性疫苗接种，从而避免了对树突状细胞的体外转导的需要。注射慢病毒载体优先转导脾树突状细胞并导致长期表达。注射编码淋巴细胞性脉络丛脑膜炎病毒（LCMV）的MHC I类限制性T细胞表位和CD40配体的慢病毒载体诱导抗原特异性溶细胞性CD8+ T淋巴细胞应答，保护小鼠免受感染。用编码LCMV MHC I类和II类T细胞表位的慢病毒载体和可溶性程序性细胞死亡1微体注射慢性感染的小鼠迅速清除病毒。通过直接注射慢病毒载体进行的疫苗接种在无菌α基序和HD结构域包含蛋白1敲除（SAMHD 1敲除）小鼠中更有效，这表明含有Vpx（一种通过诱导SAMHD 1降解来增加树突状细胞转导效率的慢病毒蛋白）的慢病毒载体将是治疗人类慢性疾病的有效策略。
Lentiviral vector–based dendritic cell vaccines induce protective T cell responses against viral infection and cancer in animal models. In this study, we tested whether preventative and therapeutic vaccination could be achieved by direct injection of antigen-expressing lentiviral vector, obviating the need for ex vivo transduction of dendritic cells. Injected lentiviral vector preferentially transduced splenic dendritic cells and resulted in long-term expression. Injection of a lentiviral vector encoding an MHC class I–restricted T cell epitope of lymphocytic choriomeningitis virus (LCMV) and CD40 ligand induced an antigen-specific cytolytic CD8+ T lymphocyte response that protected the mice from infection. The injection of chronically infected mice with a lentiviral vector encoding LCMV MHC class I and II T cell epitopes and a soluble programmed cell death 1 microbody rapidly cleared the virus. Vaccination by direct injection of lentiviral vector was more effective in sterile alpha motif and HD-domain containing protein 1–knockout (SAMHD1-knockout) mice, suggesting that lentiviral vectors containing Vpx, a lentiviral protein that increases the efficiency of dendritic cell transduction by inducing the degradation of SAMHD1, would be an effective strategy for the treatment of chronic disease in humans.
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影响因子：
82.9
作者：
通讯作者：
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影响因子：
5.8
作者：
Ellebaek, Eva;Engell-Noerregaard, Lotte;Svane, Inge Marie
通讯作者：
Svane, Inge Marie
影响因子：
30.8
作者：
AKLI, S;CAILLAUD, C;PESCHANSKI, MR
通讯作者：
PESCHANSKI, MR
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64.8
作者：
Goldstone, David C.;Ennis-Adeniran, Valerie;Webb, Michelle
通讯作者：
Webb, Michelle
小鼠肺癌最小残留模型中的树突状细胞 (DC) 疫苗；单核细胞来源的 DC 与造血干细胞来源的 DC 的比较。
影响因子：
6
作者：
Baek S;Lee SJ;Kim MJ;Lee H
通讯作者：
Lee H