Department of Infectious, Parasitic and Immune-mediated Diseases, Viale Regina Elena 299, Rome 00161, Italy.
Retrovirology. 2012 Aug 22;9:69. doi: 10.1186/1742-4690-9-69.
Integrase defective lentiviral vectors (IDLV) represent a promising delivery system for immunization purposes. Human dendritic cells (DC) are the main cell types mediating the immune response and are readily transduced by IDLV, allowing effective triggering of in vitro expansion of antigen-specific primed CD8+ T cells. However, IDLV expression in transduced DC is at lower levels than those of the integrase (IN) competent counterpart, thus requiring further improvement of IDLV for future use in the clinic.
In this paper we show that the addition of simian immunodeficiency (SIV)-Vpx protein in the vector preparation greatly improves transduction of human and simian DC, but not of murine DC, thus increasing the ability of transduced DC to act as functional antigen presenting cells, in the absence of integrated vector sequences. Importantly, the presence of SIV-Vpx allows for using lower dose of input IDLV during in vitro transduction, thus further improving the IDLV safety profile.
These results have significant implications for the development of IDLV-based vaccines.
整合酶缺陷型慢病毒载体（IDLV）代表了一种有前途的免疫接种传递系统。人树突状细胞（DC）是介导免疫反应的主要细胞类型，容易被 IDLV 转导，从而有效地触发抗原特异性初始 CD8+T 细胞的体外扩增。然而，与整合酶（IN）功能完整的对照相比，转导的 DC 中 IDLV 的表达水平较低，因此需要进一步改进 IDLV，以便将来在临床上使用。
在本文中，我们表明，在载体制备中添加猴免疫缺陷病毒（SIV）-Vpx 蛋白可显著提高人源和食蟹猴源 DC 的转导效率，但对鼠源 DC 没有作用，从而提高了转导 DC 作为功能性抗原提呈细胞的能力，而不依赖整合的载体序列。重要的是，SIV-Vpx 的存在允许在体外转导过程中使用更低剂量的输入 IDLV，从而进一步提高 IDLV 的安全性。
这些结果对基于 IDLV 的疫苗的开发具有重要意义。
