PDF(Pubmed)
Abstract：
For the development of new adenovirus (AdV)-based vectors, it is important to understand differences in immunogenicity. In a side-by-side in vitro analysis, we evaluated the effect of 40 AdV types covering human AdV (HAdV) species A through G on the expression of 11 activation markers and the secretion of 12 cytokines by AdV-transduced dendritic cells, and the effect on CD8+ T cell proliferation capacity. We found that the expression of activation markers and cytokines differed widely between the different HAdV types, and many types were able to significantly impair the proliferation capacity of CD8+ T cells. Univariate and multivariate regression analyses suggested an important role of type I interferons in mediating this suppression of CD8+ T cells, which we confirmed experimentally in a proliferation assay using a type I interferon receptor blocking antibody. Using Bayesian statistics, we calculated a prediction model that suggests HAdV types HAdV-C1, -D8, -B7, -F41, -D33, -C2, -A31, -B3 and -D65 as the most favorable candidates for vaccine vector development.
摘要：
为了开发新的基于腺病毒（AdV）的载体，了解免疫原性的差异很重要。在并排的体外分析中，我们评估了40种涵盖人类AdV（HAdV）物种A至G的AdV类型对AdV转导的树突状细胞11种活化标志物表达和12种细胞因子分泌的影响，以及对CD8+T细胞增殖能力的影响。我们发现不同HAdV类型之间的活化标志物和细胞因子的表达差异很大,和许多类型能够显著削弱CD8+T细胞的增殖能力。单变量和多变量回归分析提示I型干扰素在介导CD8+T细胞抑制中的重要作用。我们在使用I型干扰素受体阻断抗体的增殖实验中证实了这一点。使用贝叶斯统计，我们计算了一个预测模型，该模型表明HAdV型HAdV-C1，-D8，-B7，-F41，-D33，-C2，-A31，-B3和-D65是疫苗载体开发的最有利候选物。
