Non-Human Primate Core

非人类灵长类核心

• 批准号: 8294667
• 负责人: NORMAN L LETVIN
• 金额: $ 171.39万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8294667
• 关键词: AIDS/HIV problem; Antigens; Attenuated; Biological Assay; Clinical Research; Dose; Gagging; Genes; HIV-1; Immune response; Immunization; Immunology; Indiana; Intramuscular; Macaca mulatta; Monitor; Monkeys; New Jersey; Peptides; Recombinants; Route; System; T-Lymphocyte; Vaccines; Vesicular stomatitis Indiana virus; immunogenicity; neutralizing antibody; nonhuman primate; vector

To assist in selecting the optimal vector system for use in the CHAVI clinical studies, a comparison was done in rhesus monkeys between VSV and Ad to assess the magnitude and durability of vaccine-elicited T lymphocyte immune responses. The VSV vectors used in this study were made with N4CT9, a pathologically attenuated strain of the vims developed by Wyeth. The immunogenicity of these vectors was compared with that of an Eldeleted, E3-inactivated Ad5 developed by Gary Nabel, VRC and GenVec. Both vectors carried an identical HIV-1 HXBc2 gag gene insert. Ad5-seronegative monkeys were immunized at 0 and 8 weeks. Six monkeys received intramuscular inoculations of 108 pfu rVSV Indiana followed by the same dose of rVSV New Jersey, a vector that is not cross-neutralized by antibodies generated by rVSV Indiana. Six monkeys received the same immunogens delivered by the intratracheal route. Another 6 monkeys received 1011 rAd5 followed by the same dose of the same recombinant vector. Cellular immune responses were monitored by pooled peptide Elispot and ICS assays. As shown below, significant Gag-specific immune responses were only detected in the rVSVimmunized monkeys following the boosting immunization. Moreover, the immune responses elicited by the rVSV following the boosting immunization were comparable in magnitude following intratracheal and intramuscular administration, and reached the same magnitude seen following a single immunization with the rAd5 vector.

为了帮助选择用于 CHAVI 临床研究的最佳载体系统，在 在 VSV 和 Ad 之间对恒河猴进行实验，以评估疫苗诱导的 T 淋巴细胞的大小和持久性 免疫反应。本研究中使用的 VSV 载体是用 N4CT9 制成的，N4CT9 是一种病理性减毒病毒 惠氏开发的病毒株。将这些载体的免疫原性与 Eldeleted 的免疫原性进行比较， E3 灭活的 Ad5 由 Gary Nabel、VRC 和 GenVec 开发。两个载体都携带相同的 HIV-1 HXBc2 gag 基因插入。 Ad5 血清阴性猴子在第 0 周和第 8 周时进行免疫。六只猴子 接受了 108 pfu rVSV 印第安纳州肌内接种，随后接种了相同剂量的 rVSV 新泽西州， 不被 rVSV Indiana 产生的抗体交叉中和的载体。六只猴子也收到了同样的结果 通过气管内途径递送免疫原。另外 6 只猴子接受了 1011 rAd5，随后也接受了相同的治疗 相同重组载体的剂量。通过混合肽 Elispot 监测细胞免疫反应 和 ICS 检测。如下所示，仅在 rVSV 免疫组中检测到显着的 Gag 特异性免疫反应 猴子接受加强免疫后。此外，由 加强免疫后的 rVSV 气管内和肌肉内给药后的幅度相当，并达到相同的水平 使用 rAd5 载体进行单次免疫后观察到的幅度。