Non-Human Primate Core

为了帮助选择用于CHAVI临床研究的最佳载体系统，在 恒河猴VSV和Ad之间对疫苗诱导T淋巴细胞数量和持久性的评估 免疫反应。本研究中使用的VSV载体是用病理减毒的N4CT9制成的 惠氏公司开发的VIMS菌株。将这些载体的免疫原性与ELDELED的免疫原性进行了比较， E3-由Gary Nabel、VRC和GenVec开发的灭活Ad5。两个载体携带了完全相同的 HIV-1 HXBc2 Gag基因插入。分别于第0周和第8周免疫Ad5血清阴性猴。六只猴子 在印第安纳州肌肉接种108 pfu rVSV，然后在新泽西州接种相同剂量的rVSV，A 不被印第安纳州rVSV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 通过气管内途径输送的免疫原。另有6只猴子收到了1011个rAd5，随后是相同的 相同剂量的重组载体。用聚合多肽ELISPOT监测细胞免疫反应 ICS检测。如下所示，仅在免疫的rVSV中检测到显著的Gag特异性免疫反应 加强免疫后的猴子。此外，由病毒引起的免疫反应 加强免疫后的rVSV为 在气管内和肌肉内给药后，大小相当，并达到相同 RAd5载体单次免疫后所见的大小。

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.