Vacas-Córdoba Enrique, Bastida Hugo, Pion Marjorie, Hameau Aurélien, Ionov Maksim, Bryszewska Maria, Caminade Anne Marie, Majoral Jean Pierre, Muñoz-Fernández María-Ángeles
Laboratorio InmunoBiologia Molecular, Hospital General Universitario Gregorio Maranon, Madrid, Spain.
Curr Med Chem. 2014;21(16):1898-909. doi: 10.2174/0929867321666131129114022.
The objective was to study if cationic phosphorus dendrimers can be used as DC-based vaccine or adjuvant in anti-HIV-1 vaccine development when associated with HIV-1 derived peptides.
MATERIALS & METHODS: The HIV derived peptides uptake in DC and the phenotype of iDC and mDC were studied using Flow Cytometry analysis. Migration of mDC was evaluated by an in vitro chemotaxis assay. Allogenic T-cells proliferative response induced by DC was studied using Flow Cytometry assays. Cytokines production was analysed by Diaclon DIAplex Th1/Th2/Inflammation kit.
All phosphorus dendrimers showed the ability to deliver HIV-derived peptides in DC. The phosphorus dendrimers from second and third generations induced important changes in phenotype. Moreover, the treatment of mDC with the second generation dendrimer and derivated dendriplexes modified cellular migratory properties, altered their capacity to stimulate allogenic naïve T cells in vitro and impeded the production of pro-inflammatory cytokines.
The phosphorus dendrimers cannot be used as vaccines because they would not have the ability to induce an immune response. The cationic phosphorus dendrimers associated with HIV-derived peptides have the ability to deliver peptides as non-viral vectors. However, there are other potential therapeutic applications of these compounds, for instance as topical antiinflammatory agents, as compounds for allograft rejection or autoimmune diseases and as agents inducing specific tolerance with antigen-loaded DC against allergy reaction. Nevertheless, these applications need to be evaluated.
本研究旨在探讨阳离子磷树枝状大分子与HIV-1衍生肽结合时，能否用作基于树突状细胞（DC）的疫苗或佐剂，用于抗HIV-1疫苗的研发。
采用流式细胞术分析研究DC对HIV衍生肽的摄取情况以及未成熟DC（iDC）和成熟DC（mDC）的表型。通过体外趋化试验评估mDC的迁移能力。使用流式细胞术分析研究DC诱导的同种异体T细胞增殖反应。采用Diaclon DIAplex Th1/Th2/炎症检测试剂盒分析细胞因子的产生。
所有磷树枝状大分子均显示出将HIV衍生肽递送至DC的能力。第二代和第三代磷树枝状大分子可诱导表型发生重要变化。此外，用第二代树枝状大分子及其衍生的树枝状复合物处理mDC可改变细胞迁移特性，改变其体外刺激同种异体幼稚T细胞的能力，并抑制促炎细胞因子的产生。
磷树枝状大分子不能用作疫苗，因为它们没有诱导免疫反应的能力。与HIV衍生肽结合的阳离子磷树枝状大分子有能力作为非病毒载体递送肽。然而，这些化合物还有其他潜在的治疗应用，例如作为局部抗炎剂、用于同种异体移植排斥或自身免疫性疾病的化合物，以及作为用负载抗原的DC诱导针对过敏反应的特异性耐受的试剂。尽管如此，这些应用仍需评估。
