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首页> 外文会议>Conference on vaccine technology VI >SAFETY AND BIODISTRIBUTION OF SULFATED ARCHAEAL GLYCOLIPID ARCHAEOSOMES AS VACCINE ADJUVANTS
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SAFETY AND BIODISTRIBUTION OF SULFATED ARCHAEAL GLYCOLIPID ARCHAEOSOMES AS VACCINE ADJUVANTS

机译：作为疫苗辅助剂的硫酸化古糖脂的安全性和生物分布

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Archaeosomes are liposomes comprised of ether lipids derived from various archaea which, as adjuvants, can induce robust, long-lasting humoral and cell-mediated immune responses to entrapped antigens. Traditional total polar lipid (TPL) archaeosome formulations are relatively complex and semi-synthetic archaeosomes involve many synthetic steps to arrive at the final desired glycolipid composition. We have developed a novel archaeosome formulation comprising a sulfated saccharide group covalently linked to the free sn-1 hydroxyl backbone of an archaeal core lipid (sulfated S-lactosylarchaeol, SLA) mixed with uncharged glycolipid (lactosylarchaeol, LA). This new class of adjuvants can be easily synthesized and retains strong immunostimulatory activity for induction of cell-mediated immunity following systemic immunization. Herein, we demonstrate the safety of SLA/LA archaeosomes following intramuscular injection to mice and evaluate the immunogenicity, in vivo distribution and cellular uptake of antigen (ovalbumin) encapsulated into SLA/LA archaeosomes. Overall, we have found that semi-synthetic sulfated glycolipid archaeosomes are a safe and effective novel class of adjuvants capable of inducing strong antigen-specific immune responses in mice and protection against subsequent B16 melanoma tumor challenge. A key step in their mechanism of action appears to be the recruitment of immune cells to the injection site and the subsequent trafficking of antigen to local draining lymph nodes. A better understanding of the safety and mechanism of action of novel adjuvants such as archaeosomes is a key step in their advancement into clinical use.
机译：初值是由衍生自各种古代氧化的乙醚脂质的脂质体，其作为佐剂，可以诱导稳健，持久的体液和细胞介导的免疫反应对捕获的抗原。传统的总极性脂质（TPL）颅内体配方是相对复杂的并且半合成的初始体涉及许多合成步骤来到达最终所需的糖脂组合物组合物。我们开发了一种新型古代体制剂，其包含与与未充电的糖脂（Lactosylakeol，La）混合的古核心脂质（硫酸盐S-Lactosylaeol，SLA）的游离Sn-1羟基骨架共价连接的硫酸糖基团。这种新的佐剂可以很容易地合成并保留强烈的免疫刺激活性，以诱导全身免疫后细胞介导的免疫。在此，我们证明了在肌内注射到小鼠后的SLA / LA archaeoSomes的安全性，并评价免疫原性，体内分布和抗原（卵烧蛋）的细胞摄取到SLA / La archaeosomes中。总体而言，我们发现半合成的硫酸化糖脂拟初素是一种安全有效的新型佐剂，能够诱导小鼠的强烈抗原特异性免疫应答和免受随后的B16黑色素瘤肿瘤攻击。它们的作用机制的一个关键步骤似乎是将免疫细胞募集到注射部位和随后的抗原对局部排水淋巴结的抗原。更好地理解新型佐剂等新型佐剂的行动的安全和机制是他们进入临床用途的关键步骤。

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