Virologie et Immunologie Moléculaires, Institut National de la Recherche Agronomique, Jouy-en-Josas, France.
PLoS One. 2012;7(12):e52513. doi: 10.1371/journal.pone.0052513. Epub 2012 Dec 26.
Gene expression profiling of the blood cell response induced early after vaccination has previously been demonstrated to predict the immunogenicity of vaccines. In this study, we evaluated whether the analysis of the gene expression profile of skin-migrated dendritic cells (DCs) could be informative for the in vitro prediction of immunogenicity of vaccine, using canine adenovirus serotype 2 (CAV2) as vaccine vector. CAV2 has been shown to induce immunity to transgenes in several species including sheep and is an interesting alternative to human adenovirus-based vectors, based on the safety records of the parental strain in dogs and the lack of pre-existing immunity in non-host species. Skin-migrated DCs were collected from pseudo-afferent lymph in sheep. Both the CD11b(+) -type and CD103(+) -type skin-migrated DCs were transduced by CAV2. An analysis of the global gene response to CAV2 in the two skin DC subsets showed that the gene response in CD11b(+) -type DCs was far higher and broader than in the CD103(+) -type DCs. A newly released integrative analytic tool from Ingenuity systems revealed that the CAV2-modulated genes in the CD11b(+) -type DCs clustered in several activated immunogenicity-related functions, such as immune response, immune cell trafficking and inflammation. Thus gene profiling in skin-migrated DC in vitro indicates that the CD11b(+) DC type is more responsive to CAV2 than the CD103(+) DC type, and provides valuable information to help in evaluating and possibly improving viral vector vaccine effectiveness.
先前已经证明，对疫苗接种后早期诱导的血细胞反应的基因表达谱分析可预测疫苗的免疫原性。在这项研究中，我们评估了分析皮肤迁移树突状细胞（DC）的基因表达谱是否可以为疫苗免疫原性的体外预测提供信息，使用犬腺病毒血清型 2（CAV2）作为疫苗载体。CAV2 已被证明在包括绵羊在内的几种物种中诱导对转基因的免疫，并且基于亲本株在狗中的安全性记录和非宿主物种中缺乏预先存在的免疫，是一种替代人腺病毒载体的有趣选择。从绵羊的假传入淋巴中收集皮肤迁移的 DC。CAV2 转导了 CD11b(+)型和 CD103(+)型皮肤迁移 DC。对两种皮肤 DC 亚群中 CAV2 引起的全基因反应的分析表明，CD11b(+)型 DC 的基因反应远高于 CD103(+)型 DC。Ingenuity 系统发布的一种新的综合分析工具显示，CD11b(+)型 DC 中 CAV2 调节的基因聚类在几个激活的免疫相关功能中，如免疫反应、免疫细胞迁移和炎症。因此，体外皮肤迁移 DC 的基因谱分析表明，CD11b(+) DC 类型比 CD103(+) DC 类型对 CAV2 的反应更高，并提供有价值的信息，有助于评估和可能改善病毒载体疫苗的有效性。
