Aricò Eleonora, Wang Ena, Tornesello Maria Lina, Tagliamonte Maria, Lewis George K, Marincola Francesco M, Buonaguro Franco M, Buonaguro Luigi
Immunogenetics Section, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD 20892-1502, USA.
J Transl Med. 2005 Dec 29;3:45. doi: 10.1186/1479-5876-3-45.
We have recently developed a candidate HIV-1 vaccine model based on HIV-1 Pr55gag Virus-Like Particles (HIV-VLPs), produced in a baculovirus expression system and presenting a gp120 molecule from an Ugandan HIV-1 isolate of the clade A (HIV-VLPAs). The HIV-VLPAs induce in Balb/c mice systemic and mucosal neutralizing Antibodies as well as cytotoxic T lymphocytes, by intra-peritoneal as well as intra-nasal administration. Moreover, we have recently shown that the baculovirus-expressed HIV-VLPs induce maturation and activation of monocyte-derived dendritic cells (MDDCs) which, in turn, produce Th1- and Th2-specific cytokines and stimulate in vitro a primary and secondary response in autologous CD4+ T cells. In the present manuscript, the effects of the baculovirus-expressed HIV-VLPAs on the genomic transcriptional profile of MDDCs obtained from normal healthy donors have been evaluated. The HIV-VLPA stimulation, compared to both PBS and LPS treatment, modulate the expression of genes involved in the morphological and functional changes characterizing the MDDCs activation and maturation. The results of gene profiling analysis here presented are highly informative on the global pattern of gene expression alteration underlying the activation of MDDCs by HIV-VLPAs at the early stages of the immune response and may be extremely helpful for the identification of exclusive activation markers.
我们最近开发了一种基于HIV-1 Pr55gag病毒样颗粒(HIV-VLPs)的候选HIV-1疫苗模型,该颗粒在杆状病毒表达系统中产生,并呈现来自乌干达A亚型HIV-1分离株的gp120分子(HIV-VLPAs)。通过腹腔内和鼻内给药,HIV-VLPAs可在Balb/c小鼠中诱导全身和粘膜中和抗体以及细胞毒性T淋巴细胞。此外,我们最近发现,杆状病毒表达的HIV-VLPs可诱导单核细胞衍生的树突状细胞(MDDCs)成熟和活化,进而产生Th1和Th2特异性细胞因子,并在体外刺激自体CD4+ T细胞的初次和二次应答。在本手稿中,评估了杆状病毒表达的HIV-VLPAs对从正常健康供体获得的MDDCs基因组转录谱的影响。与PBS和LPS处理相比,HIV-VLPA刺激可调节参与MDDCs活化和成熟特征性形态和功能变化的基因表达。本文呈现的基因谱分析结果对于免疫应答早期HIV-VLPAs激活MDDCs所涉及的基因表达改变的全局模式具有高度信息性,并且可能对鉴定独特的激活标记物非常有帮助。