Zhou Chun-Xue, Li Dong, Chen Ying-Li, Lu Zeng-Jun, Sun Pu, Cao Yi-Mei, Bao Hui-Fang, Fu Yuan-Fang, Li Ping-Hua, Bai Xing-Wen, Xie Bao-Xia, Liu Zai-Xin
State Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Animal Virology of Ministry of Agriculture, OIE/National Foot-and-Mouth Disease Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, China.
BMC Vet Res. 2014 Jan 3;10:2. doi: 10.1186/1746-6148-10-2.
Toll-like receptor (TLR) agonists reportedly have potent antiviral and antitumor activities and may be a new kind of adjuvant for enhancing immune efficacy. Resiquimod (R848) is an imidazoquinoline compound with potent antiviral activity and functions through the TLR7/TLR8 MyD88-dependent signaling pathway. Polyinosinic-polycytidylic acid [poly(I:C)] is a synthetic analog of double-stranded RNA that induces the production of pro-inflammatory cytokines by the activation of NF-κB through TLR3. This study investigated the potential of R848 and poly(I:C) as an adjuvant 146S foot-and-mouth disease virus (FMDV) vaccine formulated with aluminum hydroxide (Al(OH)₃).
Antibody titers to FMDV and CD8+ T cells were markedly enhanced in mice immunized to 146S FMDV + Al(OH)₃ + R848 + poly(I:C) compared with mice immunized to FMDV + ISA206. IFN-γ secretion substantially increased compared with IL-4 secretion by splenic T cells stimulated with FMDV antigens in vitro, suggesting that R848, poly(I:C), and with Al(OH)₃ together biased the immune response toward a Th1-type direction.
These results indicated that the R848 and poly(I:C) together with Al(OH)₃ enhanced humoral and cellular immune responses to immunization with 146S FMDV antigens. Thus, this new vaccine formulation can be used for FMDV prevention.
据报道,Toll样受体(TLR)激动剂具有强大的抗病毒和抗肿瘤活性,可能是一种增强免疫功效的新型佐剂。瑞喹莫德(R848)是一种具有强大抗病毒活性的咪唑喹啉化合物,通过TLR7/TLR8 MyD88依赖性信号通路发挥作用。聚肌苷酸-聚胞苷酸[poly(I:C)]是双链RNA的合成类似物,通过TLR3激活NF-κB诱导促炎细胞因子的产生。本研究调查了R848和poly(I:C)作为用氢氧化铝(Al(OH)₃)配制的146S口蹄疫病毒(FMDV)疫苗佐剂的潜力。
与接种FMDV+ISA206的小鼠相比,接种146S FMDV+Al(OH)₃+R848+poly(I:C)的小鼠中,针对FMDV的抗体滴度和CD8+T细胞显著增强。与体外FMDV抗原刺激的脾T细胞分泌的IL-4相比,IFN-γ分泌大幅增加,表明R848、poly(I:C)和Al(OH)₃共同使免疫反应偏向Th1型方向。
这些结果表明,R848和poly(I:C)与Al(OH)₃一起增强了对146S FMDV抗原免疫的体液和细胞免疫反应。因此,这种新的疫苗制剂可用于预防FMDV。