Archaeosomes composed of sulfated lactosyl archaeol (SLA) glycolipids from stereoisomerically pure archaeol (1) are vaccine adjuvants that can boost immunogenicity and vaccine efficacy in preclinical models. Herein, we report a new synthesis of 2,3-bis((3,7,11,15-tetramethylhexadecyl)oxy) propan-1-ol (3) by treating (±)-3-benzyloxy-1,2-propanediol with a mesylated phytol derivative through a double nucleophilic substitution reaction, followed by reductive debenzylation. Three SLA archaeosomes from archaeols of different chiral purities were prepared, and the effect of stereochemistry on their adjuvanticity toward ovalbumin was investigated. It was found that all SLA archaeosomes induced strong humoral and cell-mediated antigen-specific immune responses following immunization of C57BL/6NCrl mice, with no significant differences, irrespective of the chiral purities. The responses were comparable or better than those obtained using mimetics of approved adjuvants. The performance of SLA archaeosomes during immunization and their lack of dependence on the stereochemistry of archaeol points toward a promising, safe, scalable, and economically viable vaccine adjuvant system.

中文翻译：

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手性纯度对考古醇基糖脂佐剂的影响

由来自立体异构纯古菌 ( 1 )的硫酸化乳糖基古菌 (SLA) 糖脂组成的古菌体是疫苗佐剂，可在临床前模型中提高免疫原性和疫苗功效。在此，我们报告了 2,3-双((3,7,11,15-四甲基十六烷基)氧基)丙-1-醇的新合成方法 ( 3) 通过双亲核取代反应用甲磺酸化的植物醇衍生物处理 (±)-3-benzyloxy-1,2-propanediol，然后进行还原脱苄基化。从不同手性纯度的古菌中制备了三种 SLA 古小体，并研究了立体化学对其对卵清蛋白的佐剂性的影响。发现在免疫 C57BL/6NCrl 小鼠后，所有 SLA 古小体均诱导了强烈的体液和细胞介导的抗原特异性免疫反应，无论手性纯度如何，均无显着差异。这些反应与使用批准的佐剂的模拟物获得的反应相当或更好。SLA 古小体在免疫过程中的表现以及它们不依赖古菌的立体化学表明了一种有前途的、安全的、可扩展的、