Deauvieau Florence, Sanchez Violette, Balas Claire, Kennel Audrey, DE Montfort Aymeric, Lang Jean, Guy Bruno
Research Department, Sanofi Pasteur, Marcy l'Etoile, France.
Am J Trop Med Hyg. 2007 Jan;76(1):144-54.
Dengue infection is an important public health issue worldwide. The ChimeriVax-Dengue (CYD) vaccine uses yellow fever (YF) 17D vaccine as a live vector. Dendritic cells (DCs) play a key role in initiating immune responses and could be an important primary target of dengue infection. We investigated in vitro the consequences of CYD infection of DCs on their activation/maturation and cytokine production. In CYD-infected DCs, we observed an up-regulation of HLA-DR, CD80, CD86, and CD83. Cells exposed to CYD secreted type I interferons, monocyte chemoattractant protein 1 (MCP-1)/CC chemokine ligand 2 (CCL-2), interleukin-6 (IL-6), and low amounts of tumor necrosis factor-alpha (TNF-alpha), but no IL-10, IL-12, or IL-1alpha. Parental dengue viruses induced a similar array of cytokines, but more TNF-alpha, less IL-6, and less MCP-1/CCL-2 than induced by CYD. Chimeras thus induced DCs maturation and a controlled response accompanied by limited inflammatory cytokine production and consistent expression of anti-viral interferons, in agreement with clinical observations of safety and immunogenicity.
登革热感染是全球重要的公共卫生问题。嵌合登革热疫苗（CYD）以黄热病（YF）17D疫苗作为活载体。树突状细胞（DCs）在启动免疫反应中起关键作用，可能是登革热感染的重要初始靶点。我们在体外研究了CYD感染DCs对其活化/成熟及细胞因子产生的影响。在CYD感染的DCs中，我们观察到HLA-DR、CD80、CD86和CD83上调。暴露于CYD的细胞分泌I型干扰素、单核细胞趋化蛋白1（MCP-1）/CC趋化因子配体2（CCL-2）、白细胞介素-6（IL-6）以及少量肿瘤坏死因子-α（TNF-α），但不分泌IL-10、IL-12或IL-1α。亲本登革热病毒诱导产生类似的细胞因子谱，但与CYD相比，TNF-α更多，IL-6和MCP-1/CCL-2更少。因此，嵌合体诱导DCs成熟并引发可控反应，伴有有限的炎性细胞因子产生以及抗病毒干扰素的持续表达，这与安全性和免疫原性的临床观察结果一致。
