Cellular immune responses play a fundamental role in controlling viral replication and AIDS progression in human immunodeficiency virus (HIV)-infected subjects and in simian immunodeficiency virus (SIV)-infected macaques. Integrase defective lentiviral vector (IDLV) represents a promising vaccine candidate, inducing functional and durable immune responses in mice and non-human primates. Here, we designed HIV- and SIV-based IDLVs to express the HIVACAT T cell immunogen (HTI), a mosaic antigen designed to cover vulnerable sites in HIV-1 Gag, Pol, Vif, and Nef. We observed that HTI expression during lentiviral vector production interfered profoundly with IDLV particles release because of sequestration of both HIV- and SIV-Gag proteins in the cytoplasm of the vector-producing cells. However, modifications in IDLV design and vector production procedures greatly improved recovery of both HIV- and SIV-based IDLV-HTI. Immunization experiments in BALB/c mice showed that both IDLVs elicited HTI-specific T cell responses. However, immunization with HIV-based IDLV elicited also a T cell response toward exogenous HIV proteins in IDLV particles, suggesting that SIV-based IDLV may be a preferable platform to assess the induction of transgene-specific immune responses against rationally designed HIV structural antigens. These data support the further evaluation of IDLV as an effective platform of T cell immunogens for the development of an effective HIV vaccine.

细胞免疫应答在控制人类免疫缺陷病毒（HIV）感染的受试者和猿猴免疫缺陷病毒（SIV）感染的猕猴中控制病毒复制和AIDS进展中起着基本作用。整合酶缺陷型慢病毒载体（IDLV）代表了一种有前途的疫苗候选物，可在小鼠和非人灵长类动物中诱导功能性和持久性免疫应答。在这里，我们设计了基于HIV和SIV的IDLV，以表达HIVACAT T细胞免疫原（HTI），这是一种镶嵌抗原，旨在覆盖HIV-1 Gag，Pol，Vif和Nef中的脆弱部位。我们观察到，慢病毒载体生产过程中的HTI表达对IDLV颗粒的释放产生了深远的干扰，因为在载体生产细胞的细胞质中螯合了HIV和SIV-Gag蛋白。然而，对IDLV设计和载体生产程序的修改大大提高了基于HIV和基于SIV的IDLV-HTI的回收率。在BALB / c小鼠中进行的免疫实验表明，两种IDLV均可引起HTI特异性T细胞应答。但是，用基于HIV的IDLV免疫也会引起针对IDLV颗粒中外源HIV蛋白的T细胞应答，这表明基于SIV的IDLV可能是评估针对合理设计的HIV结构抗原的转基因特异性免疫应答诱导的优选平台。这些数据支持进一步评估IDLV作为开发有效HIV疫苗的T细胞免疫原的有效平台。基于HIV的IDLV免疫还引发了针对IDLV颗粒中外源HIV蛋白的T细胞应答，这表明基于SIV的IDLV可能是评估针对合理设计的HIV结构抗原的转基因特异性免疫应答诱导的优选平台。这些数据支持进一步评估IDLV作为开发有效HIV疫苗的T细胞免疫原的有效平台。基于HIV的IDLV免疫还引发了针对IDLV颗粒中外源HIV蛋白的T细胞应答，这表明基于SIV的IDLV可能是评估针对合理设计的HIV结构抗原的转基因特异性免疫应答诱导的优选平台。这些数据支持进一步评估IDLV作为开发有效HIV疫苗的T细胞免疫原的有效平台。