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首页> 外文期刊>Vaccine >Vaccines delivered by integration-deficient lentiviral vectors targeting dendritic cells induces strong antigen-specific immunity.
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Vaccines delivered by integration-deficient lentiviral vectors targeting dendritic cells induces strong antigen-specific immunity.

机译:靶向树突状细胞的整合缺陷型慢病毒载体提供的疫苗可诱导强抗原特异性免疫。

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摘要

We report a study of an integration-deficient lentiviral vector (IDLV) enveloped with a Sindbis virus glycoprotein mutant (SVGmu) capable of selectively binding to dendritic cells (DCs) for its potential as a vaccine carrier. The in vitro assays showed that the D64V point mutation in the catalytic domain of HIV-1 integrase efficiently inhibited the integration of the transgene upon vector transduction, while the targeting specificity of the vector to preferentially transduce and mediate durable expression in DCs was maintained. Substantial immune responses in C57BL/6 mice and complete protection against a challenge with the C57BL/6 thymoma EG.7 tumor expressing a delivered ovalbumin (OVA) antigen in mice have been achieved through the direct injection of the DC-directed IDLV encoding OVA. Thus, this DC-directed IDLV system represents a promising and efficient vector platform with remarkably improved safety for the future development of DC-based immunotherapy.
机译:我们报告了一项关于整合缺陷型慢病毒载体(IDLV)的研究,该载体被Sindbis病毒糖蛋白突变体(SVGmu)包裹,能够选择性地结合树突状细胞(DCs)作为疫苗载体。 体外分析表明,HIV-1整合酶催化域中的D64V点突变在载体转导时有效抑制了转基因的整合,而载体的靶向特异性优先转导和介导了持久性DC中的表达得以维持。通过直接注射编码DC的IDLV编码的IDLV,已在小鼠中实现了C57BL / 6小鼠的实质性免疫应答和针对表达表达的卵白蛋白(OVA)抗原的C57BL / 6胸腺瘤EG.7肿瘤的完全保护。因此,该DC定向IDLV系统代表了一个有前途的高效载体平台,对于基于DC的免疫疗法的未来发展具有显着提高的安全性。

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