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手性纯度对基于古生菌醇的糖脂佐剂活性的影响。

Effect of Chiral Purity on Adjuvanticity of Archaeol-Based Glycolipids.

机构信息

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.

出版信息

J Med Chem. 2022 Jun 23;65(12):8332-8344. doi: 10.1021/acs.jmedchem.2c00072. Epub 2022 Jun 3.


DOI:10.1021/acs.jmedchem.2c00072
PMID:35658102
Abstract

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.

摘要

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。

相似文献

[1]
Effect of Chiral Purity on Adjuvanticity of Archaeol-Based Glycolipids.

J Med Chem. 2022-6-23

[2]
The Synergistic Effects of Sulfated Lactosyl Archaeol Archaeosomes When Combined with Different Adjuvants in a Murine Model.

Pharmaceutics. 2021-2-2

[3]
Sulfated lactosyl archaeol (SLA) archaeosomes as a vaccine adjuvant.

Hum Vaccin Immunother. 2024-12-31

[4]
Sulfated archaeol glycolipids: Comparison with other immunological adjuvants in mice.

PLoS One. 2018-12-4

[5]
Mechanistic insight into the induction of cellular immune responses by encapsulated and admixed archaeosome-based vaccine formulations.

Hum Vaccin Immunother. 2020-9-1

[6]
Generation of a Liposomal Vaccine Adjuvant Based on Sulfated S-Lactosylarchaeol (SLA) Glycolipids.

Methods Mol Biol. 2022

[7]
Safety and biodistribution of sulfated archaeal glycolipid archaeosomes as vaccine adjuvants.

Hum Vaccin Immunother. 2018-1-30

[8]
Sulfated Lactosyl Archaeol Archaeosomes Synergize with Poly(I:C) to Enhance the Immunogenicity and Efficacy of a Synthetic Long Peptide-Based Vaccine in a Melanoma Tumor Model.

Pharmaceutics. 2021-2-12

[9]
Tuning the immune response: sulfated archaeal glycolipid archaeosomes as an effective vaccine adjuvant for induction of humoral and cell-mediated immunity towards the SARS-CoV-2 Omicron variant of concern.

Front Immunol. 2023

[10]
Assessment of stability of sulphated lactosyl archaeol archaeosomes for use as a vaccine adjuvant.

J Liposome Res. 2021-9

引用本文的文献

[1]
Sulfated lactosyl archaeol (SLA) archaeosomes as a vaccine adjuvant.

Hum Vaccin Immunother. 2024-12-31

[2]
Sulfated Lactosyl Archaeol Archaeosome-Adjuvanted Vaccine Formulations Targeting Rabbit Hemorrhagic Disease Virus Are Immunogenic and Efficacious.

Vaccines (Basel). 2023-5-31

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