Zhang Wen-Wei, Matlashewski Greg
Department of Microbiology and Immunology, 3775 University Street, McGill University, Montreal, Quebec H2A 2B4, Canada.
Infect Immun. 2008 Aug;76(8):3777-83. doi: 10.1128/IAI.01527-07. Epub 2008 May 12.
Activation of Toll-like receptors (TLRs) on antigen-presenting cells of the innate immune system initiates, amplifies, and directs the antigen-specific acquired immune response. Ligands that stimulate TLRs therefore represent potential vaccine adjuvants. In the present study, we determined whether imiquimod and its related compound R848, which are TLR7 and/or TLR8 agonists, represent potential vaccine adjuvants when delivered topically, subcutaneously, or intramuscularly. Using the Leishmania major infection model in BALB/c mice, vaccination with crude Leishmania antigen was not protective against subsequent challenge infection unless it was administered with R848 or a topical application of imiquimod containing cream on the skin. Subcutaneous vaccination with these adjuvants mediated a TH1 response against L. major antigen, which appeared to suppress the TH2 response following a challenge infection. Protective immunity was generated following subcutaneous vaccination but not intramuscular vaccination. These observations suggest that topically administered imiquimod or subcutaneously injected R848 represent potential vaccine adjuvants to enhance the TH1 response, which can be used with existing or new vaccine formulations.
天然免疫系统抗原呈递细胞上的Toll样受体（TLR）激活可启动、放大并指导抗原特异性获得性免疫反应。因此，刺激TLR的配体代表了潜在的疫苗佐剂。在本研究中，我们确定了咪喹莫特及其相关化合物R848（它们是TLR7和/或TLR8激动剂）在经皮、皮下或肌肉注射给药时是否代表潜在的疫苗佐剂。使用BALB/c小鼠的硕大利什曼原虫感染模型，用粗制利什曼原虫抗原进行疫苗接种并不能预防随后的攻击感染，除非同时给予R848或在皮肤上局部应用含咪喹莫特的乳膏。用这些佐剂进行皮下疫苗接种介导了针对硕大利什曼原虫抗原的TH1反应，这似乎抑制了攻击感染后的TH2反应。皮下疫苗接种后产生了保护性免疫，但肌肉注射疫苗接种后未产生。这些观察结果表明，局部应用咪喹莫特或皮下注射R848代表了增强TH1反应的潜在疫苗佐剂，可与现有或新的疫苗制剂一起使用。
