Gutjahr Alice, Papagno Laura, Nicoli Francesco, Lamoureux Alain, Vernejoul Fabienne, Lioux Thierry, Gostick Emma, Price David A, Tiraby Gérard, Perouzel Eric, Appay Victor, Verrier Bernard, Paul Stéphane
InvivoGen, 31400 Toulouse, France.
Laboratoire de Biologie Tissulaire et d'Ingénierie Thérapeutique, UMR5305, Université Lyon 1, CNRS, 69007 Lyon, France.
J Immunol. 2017 Jun 1;198(11):4205-4209. doi: 10.4049/jimmunol.1602131. Epub 2017 Apr 21.
TLR agonists are currently being developed and tested as adjuvants in various formulations to optimize the immunogenicity and efficacy of vaccines. The aim of this study was to evaluate the immunostimulatory properties of a novel compound incorporating covalently linked moieties designed to stimulate both TLR2 and TLR7. This dual TLR2/TLR7 agonist induced the maturation of dendritic cells and primed substantial populations of cytolytic and highly polyfunctional effector CD8 T cells in vitro, and safely potentiated the immunogenic properties of a nanoparticulate Ag in vivo, eliciting humoral responses with a balanced T1/T2 profile in mice. Collectively, these data reveal the potential utility of chimeric adjuvants with synergistic activities mediated via TLRs.
Toll样受体(TLR)激动剂目前正作为佐剂在各种制剂中进行研发和测试,以优化疫苗的免疫原性和效力。本研究的目的是评估一种新型化合物的免疫刺激特性,该化合物包含共价连接的部分,旨在同时刺激TLR2和TLR7。这种双重TLR2/TLR7激动剂在体外诱导树突状细胞成熟,并启动大量细胞毒性和高度多功能效应性CD8 T细胞群体,并且在体内安全地增强了纳米颗粒抗原的免疫原性,在小鼠中引发具有平衡T1/T2特征的体液反应。总体而言,这些数据揭示了通过TLR介导具有协同活性的嵌合佐剂的潜在用途。