Patchett Amanda L, Tovar Cesar, Corcoran Lynn M, Lyons A Bruce, Woods Gregory M
Menzies Institute for Medical Research, University of Tasmania, Hobart 7000, Tasmania, Australia.
Menzies Institute for Medical Research, University of Tasmania, Hobart 7000, Tasmania, Australia.
Dev Comp Immunol. 2017 Nov;76:352-360. doi: 10.1016/j.dci.2017.07.004. Epub 2017 Jul 6.
Devil facial tumour disease (DFTD) describes two genetically distinct transmissible tumours that pose a significant threat to the survival of the Tasmanian devil. A prophylactic vaccine could protect devils from DFTD transmission. For this vaccine to be effective, potent immune adjuvants will be required. Toll-like receptors (TLRs) promote robust immune responses in human cancer studies and are highly conserved across mammalian species. In this study, we investigated the proficiency of TLR ligands for immune activation in the Tasmanian devil using in vitro mononuclear cell stimulations and in vivo immunisation trials with a model antigen. We identified two such TLR ligands, polyICLC (Hiltonol) (TLR3) and imiquimod (TLR7), that in combination induced significant IFNγ production from Tasmanian devil lymphocytes in vitro. Immunisation with these ligands and the model antigen keyhole limpet haemocyanin activated robust antigen-specific primary, secondary and long-term memory IgG responses. Our results support the conserved nature of TLR signaling across mammalian species. PolyICLC and imiquimod will be trialed as immune adjuvants in future DFTD vaccine formulations.
袋獾面部肿瘤病（DFTD）指的是两种基因不同的可传播肿瘤，对袋獾的生存构成重大威胁。预防性疫苗可以保护袋獾免受DFTD传播。要使这种疫苗有效，将需要强效免疫佐剂。Toll样受体（TLR）在人类癌症研究中可促进强大的免疫反应，并且在哺乳动物物种中高度保守。在本研究中，我们使用体外单核细胞刺激和体内模型抗原免疫试验，研究了TLR配体在袋獾中激活免疫的能力。我们鉴定出两种这样的TLR配体，聚肌胞苷酸（聚肌胞苷酸-聚左旋赖氨酸-羧甲基纤维素）（希尔顿诺）（TLR3）和咪喹莫特（TLR7），它们组合后可在体外诱导袋獾淋巴细胞产生大量γ干扰素。用这些配体和模型抗原钥孔戚血蓝蛋白进行免疫，可激活强大的抗原特异性初次、二次和长期记忆IgG反应。我们的结果支持TLR信号在哺乳动物物种中的保守性质。聚肌胞苷酸-聚左旋赖氨酸-羧甲基纤维素和咪喹莫特将在未来的DFTD疫苗制剂中作为免疫佐剂进行试验。
