Non-Human Primate Core

非人类灵长类核心

• 批准号: 8105387
• 负责人: NORMAN L LETVIN
• 金额: $ 124.33万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8105387
• 关键词: Antigens; Attenuated; Biological Assay; Clinical Research; Dose; Gagging; Genes; HIV-1; Immune response; Immunization; 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.

为了协助选择用于CHAVI临床研究的最佳矢量系统，在 VSV和AD之间的恒河猴，以评估疫苗吸收的T淋巴细胞的幅度和耐用性 免疫反应。本研究中使用的VSV载体是用N4CT9制成的，这是一种病理减弱的 Wyeth开发的VIM的菌株。将这些载体的免疫原性与详细的载体进行了比较 E3灭活的AD5由Gary Nabel，VRC和Genvec开发。两个向量都带有相同的 HIV-1 HXBC2 GAG基因插入物。 AD5-副猴子在0和8周时被免疫。六只猴子 接受了108个PFU RVSV印第安纳州的肌内接种，然后接受相同剂量的RVSV新泽西 载体未由RVSV印第安纳州产生的抗体交叉中和。六只猴子收到相同的 气管内路线传递的免疫原子。另外6只猴子收到1011 rad5，然后是相同的 同一重组载体的剂量。通过合并的肽ELISPOT监测细胞免疫反应 和ICS分析。如下所示，仅在RVSVimmunized中检测到明显的GAG特异性免疫反应 促进免疫接种后的猴子。此外，由 促进免疫后的RVSV是 气管内和肌内给药后的幅度可比，并达到相同 用RAD5载体进行单个免疫后，观察到幅度。