Evaluation of adenovirus vectors containing serotype 35 fibers for vaccination
Evaluation of adenovirus vectors containing serotype 35 fibers for vaccination
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DOI：
10.1016/j.ymthe.2005.12.008
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发表时间：
2006-04-01
影响因子：
12.4
通讯作者：
Lieber, A
中科院分区：
文献类型：
--
作者：
DiPaolo, N;Ni, S;Lieber, A
与常用的基于血清型5的腺病毒（Ad）载体相反，含有源自B组血清型35（Ad 5/35）的纤维的Ad有效地离体扩增人DC，并且在静脉内注射到狒狒中后似乎靶向抗原呈递细胞。基于此，Ad 5/35载体可能是用于免疫治疗和疫苗接种的有价值的工具。另一方面，许多研究表明，通过B组Ad受体CD 46的信号传导可以引起耐受或免疫抑制。由于小鼠不以类似人类的模式表达CD 46，我们研究了Ad 5/35在以与人类相似的模式和水平表达CD 46的转基因小鼠中的体内特性。超敏反应测定和调节性T细胞和T细胞应答的频率分析并没有表明AdS/35注射对宿主的免疫系统产生有害影响。表达模型抗原的Ac 15/35载体能够在肌内注射后引发针对测试抗原的强T细胞应答。总体而言，与Ac 15载体相比，Ad 5/35载体具有更好的安全性，这反映在促炎细胞因子的血清水平较低。
In contrast to commonly used serotype 5-based adenovirus (Ad) vectors, Ad's containing fibers derived from B-group serotype 35 (Ad5/35) efficiently transduce human DCs ex vivo and appear to target antigen-presenting cells after intravenous injection into baboons. Based on this, Ad5/35 vectors could be valuable tools for immunotherapy and vaccination. On the other hand, a number of studies indicate that signaling through the B-group Ad receptor, CD46, can cause tolerance or immunosuppression. Since mice do not express CD46 in a human-like pattern, we studied the in vivo properties of Ad5/35 in transgenic mice that express CD46 in a pattern and at a level similar to those of humans. Hypersensitivity assays and analyses of frequencies of regulatory T cells and T cell responses did not indicate that AdS/35 injection exerts detrimental effects on the host's immune system. An Ac15/35 vector expressing a model antigen was able to trigger a strong T cell response against the test antigen after intramuscular injection. Overall, compared to Ac15 vectors, Ad5/35 vectors had a better safety profile, reflected by lower serum levels of proinflammatory cytokines.