a Human Health Therapeutics , National Research Council Canada , Ottawa , Canada.
Hum Vaccin Immunother. 2017 Dec 2;13(12):2772-2779. doi: 10.1080/21645515.2017.1316912. Epub 2017 May 24.
Archaeosomes are liposomal vesicles composed of ether glycerolipids unique to the domain of Archaea. Unlike conventional ester-linked liposomes, archaeosomes exhibit high stability and possess strong adjuvant and immunostimulatory properties making them an attractive vaccine delivery vehicle. Traditionally comprised of total polar lipids (TPL) or semi-synthetic phospho-glycerolipids of ether-linked isoprenoid phytanyl cores with varied glycol- and amino-head groups, archaeosomes can induce robust and long-lasting humoral and cell-mediated immune responses against antigenic cargo and provide protection in murine models of infectious disease and cancer. However, traditional TPL archaeosome formulations are relatively complex comprising several lipid species. Semi-synthetic archaeosomes tested previously contain a combination of several phospho-glycolipids (negative and neutral charged) to produce a stable, uniform-sized liposome formulation. Moreover, they involve many synthetic steps to arrive at the final desired glycolipid composition. Herein, we present a novel adjuvant formulation comprising a sulfated saccharide group covalently linked to the free sn-1 hydroxyl backbone of an archaeal core lipid (sulfated S-lactosylarchaeol, SLA). SLA individually or mixed with uncharged glyolipid (lactosylarchaeol, LA) constituted efficacious carrier vesicles for entrapped antigens (ovalbumin or melanoma associated tyrosinase-related protein 2 [TRP-2]) and induction of strong cell-mediated responses in mice and protection against subsequent B16 melanoma tumor challenge. Thus, semi-synthetic sulfated glycolipid archaeosomes represent a new class of adjuvants that will potentially ease manufacturing and scale-up, while retaining immunostimulatory activity.
archaeosomes 是由独特于古菌域的醚甘油脂组成的脂质体囊泡。与传统的酯键连接的脂质体不同， archaeosomes 表现出高稳定性，并具有强大的佐剂和免疫刺激特性，使其成为一种有吸引力的疫苗传递载体。传统上由总极性脂质 (TPL) 或半合成的醚连接的异戊二烯植烷核心的磷酸甘油脂组成，具有不同的糖基和氨基头基团， archaeosomes 可以诱导针对抗原货物的强大和持久的体液和细胞介导的免疫反应，并在感染性疾病和癌症的小鼠模型中提供保护。然而，传统的 TPL archaeosome 制剂相对复杂，包含几种脂质种类。以前测试的半合成 archaeosome 含有几种磷酸糖脂 (带负电荷和带正电荷) 的组合，以产生稳定、均匀大小的脂质体制剂。此外，它们涉及许多合成步骤才能达到最终所需的糖脂组成。在此，我们提出了一种新型佐剂制剂，由共价连接到古菌核心脂质游离 sn-1 羟基主链的硫酸化糖基基团组成 (硫酸化 S-乳糖基 archaeol, SLA)。SLA 单独或与不带电荷的糖脂 (乳糖基 archaeol, LA) 混合构成有效的载体囊泡，用于包封抗原 (卵清蛋白或黑色素瘤相关酪氨酸酶相关蛋白 2 [TRP-2])，并在小鼠中诱导强烈的细胞介导反应，并保护其免受随后的 B16 黑色素瘤肿瘤挑战。因此，半合成的硫酸化糖脂 archaeosomes 代表了一类新的佐剂，它们有可能简化制造和扩大规模，同时保持免疫刺激活性。
