Department of Comparative Pathobiology, School of Veterinary Medicine, Purdue University, West Lafayette, IN, USA.
Gene Ther. 2010 May;17(5):634-42. doi: 10.1038/gt.2010.1. Epub 2010 Feb 18.
The absence of preexisting immunity against porcine adenovirus (Ad) serotype 3 (PAd3) and bovine Ad serotype 3 (BAd3) in humans makes them attractive alternatives to human Ad serotype 5 (HAd5) vectors. To determine whether there is significant cross-reactivity among HAd5, BAd3 and PAd3 at the level of cell-mediated immune responses, BALB/c mice were inoculated intraperitoneally with wild-type (WT) or replication-defective (RD) HAd5, BAd3 or PAd3. After 35 days of the first inoculation, cross-reactive CD8+ cytotoxic T cells, as well as CD4+ Th1- and Th2-helper T cells, in the spleen were analyzed by enzyme-linked-immunospot, flow cytometry and cytotoxic T lymphocyte assays. Virus-neutralization assays were used to evaluate humoral cross-reactivity. CD8+ or CD4+ T cells primed with WT or RD HAd5, PAd3 or BAd3 showed significant (P<0.005) reactivity with homologous Ad antigens, whereas only minimal cross-reactivity was observed on stimulation with heterologous Ad antigens. Ad-neutralizing antibodies were found to be homologous Ad specific. Overall, these results suggest that there is no significant immunological cross-reactivity among HAd5, BAd3 and PAd3, thereby supporting the rationale for the use of BAd3 and PAd3 as alternative HAd vectors to circumvent anti-HAd immunity in humans.
在人类中，针对猪腺病毒（Ad）血清型 3（PAd3）和牛 Ad 血清型 3（BAd3）的预先存在的免疫缺失使其成为人类 Ad 血清型 5（HAd5）载体的替代品。为了确定 HAd5、BAd3 和 PAd3 在细胞介导的免疫反应水平上是否存在显著的交叉反应性，BALB/c 小鼠经腹腔接种野生型（WT）或复制缺陷型（RD）HAd5、BAd3 或 PAd3。第一次接种后 35 天，通过酶联免疫斑点、流式细胞术和细胞毒性 T 淋巴细胞测定分析脾中的交叉反应性 CD8+细胞毒性 T 细胞以及 CD4+Th1 和 Th2 辅助 T 细胞。病毒中和测定用于评估体液交叉反应性。用 WT 或 RD HAd5、PAd3 或 BAd3 致敏的 CD8+或 CD4+T 细胞对同源 Ad 抗原表现出显著的（P<0.005）反应性，而用异源 Ad 抗原刺激时仅观察到最小的交叉反应性。发现 Ad 中和抗体是同源 Ad 特异性的。总体而言，这些结果表明 HAd5、BAd3 和 PAd3 之间没有明显的免疫交叉反应性，从而支持使用 BAd3 和 PAd3 作为替代 HAd 载体以规避人类中针对 HAd 的免疫的原理。
