Panilaitis Bruce, Johri Atul, Blank Walter, Kaplan David, Fuhrman Juliet
Department of Biology,Tufts University, Medford, Massachusetts 02155, USA.
Clin Diagn Lab Immunol. 2002 Nov;9(6):1240-7. doi: 10.1128/cdli.9.6.1240-1247.2002.
Several promising adjuvant candidates have been studied over the past 75 years; however, only alum is currently approved for human use. The complex acylated polysaccharide emulsan, secreted from Acinetobacter calcoaceticus, represents a new candidate. Unique features of this family of polymers are their amenability to structural tailoring and their emulsification behavior. We demonstrate that emulsan activates macrophages in a dose-dependent manner. This activation is dependent on the presence of the fatty acid side chains that decorate the polysaccharide backbone, and, furthermore, the level of activation can be affected by changes in the chemical characteristics of emulsan structural variants. One emulsan variant was examined in a classical hapten carrier immunization protocol and demonstrated significant adjuvant activity as determined by hapten-specific antibody titers. This immune response was characterized by a high immunoglobulin G2a titer, consistent with a Th1 response. The significant immunopotentiation demonstrated by this complex polymer establishes emulsan as an exciting new candidate adjuvant. Furthermore, by manipulating the chemical structure of this compound, we can explore the physical basis of pattern recognition receptors and macrophage activation.
在过去75年里,人们研究了几种有前景的佐剂候选物;然而,目前只有明矾被批准用于人类。从醋酸钙不动杆菌分泌的复杂酰化多糖乳化剂是一种新的候选物。这类聚合物的独特之处在于它们易于进行结构调整以及具有乳化行为。我们证明乳化剂以剂量依赖的方式激活巨噬细胞。这种激活取决于修饰多糖主链的脂肪酸侧链的存在,此外,激活水平会受到乳化剂结构变体化学特性变化的影响。在经典的半抗原载体免疫方案中检测了一种乳化剂变体,通过半抗原特异性抗体滴度测定显示出显著的佐剂活性。这种免疫反应的特征是高免疫球蛋白G2a滴度,与Th1反应一致。这种复合聚合物所显示的显著免疫增强作用确立了乳化剂作为一种令人兴奋的新型佐剂候选物。此外,通过操纵该化合物的化学结构,我们可以探索模式识别受体和巨噬细胞激活的物理基础。