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.

为了帮助选择CHAVI临床研究中使用的最佳载体系统， VSV和Ad之间的恒河猴，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N4 CT 9制备的，N4 CT 9是一种病理减毒的VSV载体。 惠氏公司研制的病毒株。将这些载体的免疫原性与El缺失的载体的免疫原性进行比较， E3失活的Ad 5，由加里·纳贝尔、VRC和GenVec开发。两个载体都携带着相同的 HIV-1 HXBc 2 gag基因插入片段。在第0周和第8周对Ad 5血清阴性猴进行免疫。六只猴子 肌肉注射108 pfu rVSV印第安纳州，然后注射相同剂量的rVSV新泽西， 不被rVSV印第安纳州产生的抗体交叉中和的载体。六只猴子接受了相同的 免疫原通过肠内途径递送。另外6只猴接受1011 rAd 5，随后接受相同的 剂量相同的重组载体。通过合并肽Elispot监测细胞免疫反应 和ICS测定。如下所示，仅在rVSV免疫的小鼠中检测到显著的GAG特异性免疫应答。 加强免疫后的猴子。此外，免疫反应引起的 加强免疫后的rVSV为 经皮和肌内给药后的幅度相当，并达到相同的 在用rAd 5载体单次免疫后观察到的幅度。