Aquatic and Crop Resource Development, National Research Council of Canada, 6100 Royalmount Avenue, Montreal, Quebec H4P 2R2, Canada.
Aquatic and Crop Resource Development, National Research Council of Canada, 1411 Oxford Street, Halifax, Nova Scotia B3H 3Z1, Canada.
J Med Chem. 2022 Jun 23;65(12):8332-8344. doi: 10.1021/acs.jmedchem.2c00072. Epub 2022 Jun 3.
Archaeosomes composed of sulfated lactosyl archaeol (SLA) glycolipids from stereoisomerically pure archaeol () 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 () 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.
由立体纯 archaeol () 的硫酸化乳糖基 archaeol (SLA) 糖脂组成的 archaeosomes 是疫苗佐剂,可在临床前模型中增强免疫原性和疫苗效力。在此,我们报告了通过双亲核取代反应,用甲磺酸化植醇衍生物处理(±)-3-苄氧基-1,2-丙二醇,随后进行脱苄基还原,来合成 2,3-双((3,7,11,15-四甲基十六烷基)氧基)丙-1-醇 () 的新方法。从不同手性纯度的 archaeols 制备了三种 SLA archaeosomes,并研究了立体化学对手性对卵清蛋白佐剂活性的影响。结果发现,所有 SLA archaeosomes 在免疫 C57BL/6NCrl 小鼠后均诱导了强烈的体液和细胞介导的抗原特异性免疫应答,与手性纯度无关,没有显著差异。这些反应与已批准佐剂的类似物相当或更好。SLA archaeosomes 在免疫过程中的表现及其对手性 archaeol 的依赖性缺失表明,这是一种有前途、安全、可扩展且经济可行的疫苗佐剂系统。
J Med Chem. 2022-6-23
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