Denkinger Michael, Shive Carey L, Pantenburg Birte, Forsthuber Thomas G
Institute of Pathology, School of Medicine, Case Western Reserve University, 2109 Adelbert Road, Cleveland, OH 44106, USA.
Int Immunopharmacol. 2004 Jan;4(1):15-24. doi: 10.1016/j.intimp.2003.09.004.
Aluminum hydroxide and incomplete Freund's adjuvant (IFA) are the only adjuvants approved for human use. Both are T helper 2 (Th2) adjuvants, however, T helper 1 (Th1) immunity is induced if microbial products such as mycobacteria, CpG's, or bacterial toxins are included in the adjuvant preparation. The usefulness of bacterial toxins, such as Pertussis toxin (PT) or Cholera toxin (CT), as adjuvants for human vaccination is limited by toxic side effects and high immunogenicity. Hence, we asked whether or not the adjuvant activity of bacterial toxins on Th1 and Th2 immunity could be mimicked by chemical compounds of small molecular weight and less immunogenicity. In the present study, we show that Suramin, a small molecular weight naphthylurea, which mainly acts on G-proteins and on P2X/P2Y receptors, promotes expansion of hen eggwhite lysozyme (HEL)-specific Th1 and Th2 cells upon immunization of BALB/c mice with HEL in aluminum hydroxide (alum). The results indicated that the adjuvant effects of Suramin on T cell responses were mediated by enhancing the expression of MHC class II and costimulatory molecules on antigen presenting cells (APCs), and by increasing their pro-inflammatory cytokine production. Together, the results suggest that small molecular weight compounds such as Suramin could be used as alternative vaccine adjuvants.
氢氧化铝和不完全弗氏佐剂（IFA）是仅有的被批准用于人体的佐剂。二者均为辅助性T细胞2（Th2）佐剂，然而，如果佐剂制剂中包含分枝杆菌、CpG或细菌毒素等微生物产物，则会诱导辅助性T细胞1（Th1）免疫。诸如百日咳毒素（PT）或霍乱毒素（CT）等细菌毒素作为人体疫苗佐剂的效用受到毒副作用和高免疫原性的限制。因此，我们探究了低分子量且免疫原性较低的化合物是否能够模拟细菌毒素对Th1和Th2免疫的佐剂活性。在本研究中，我们发现苏拉明，一种主要作用于G蛋白和P2X/P2Y受体的低分子量萘基脲，在用氢氧化铝（明矾）中的溶菌酶（HEL）免疫BALB/c小鼠后，可促进卵清溶菌酶（HEL）特异性Th1和Th2细胞的扩增。结果表明，苏拉明对T细胞反应的佐剂作用是通过增强抗原呈递细胞（APC）上MHC II类分子和共刺激分子的表达，以及增加其促炎细胞因子的产生来介导的。总之，这些结果表明，诸如苏拉明等低分子量化合物可用作替代疫苗佐剂。
