Human Health Therapeutics, National Research Council Canada, Ottawa, ON K1A 0R6, Canada.
Nanotechnology Research Center, National Research Council Canada, Edmonton, AB T6G 2M9, Canada.
Int J Pharm. 2019 Apr 20;561:187-196. doi: 10.1016/j.ijpharm.2019.02.041. Epub 2019 Mar 2.
Archaeosomes are liposomes composed of natural or synthetic archaeal lipids that can be used as adjuvants to induce strong long-lasting humoral and cell-mediated immune responses against entrapped antigen. However, the entrapment efficiency of antigen within archaeosomes constituted using standard liposome forming methodology is often only 5-40%. In this study, we evaluated different formulation methods using a simple semi-synthetic archaeal lipid (SLA, sulfated lactosyl archaeol) and two different antigens, ovalbumin (OVA) and hepatitis B surface antigen (HBsAg). Antigen was entrapped within archaeosomes using the conventional thin film hydration-rehydration method with or without removal of non-entrapped antigen, or pre-formed empty archaeosomes were simply admixed with an antigen solution. Physicochemical characteristics were determined (size distribution, zeta potential, vesicle morphology and lamellarity), as well as location of antigen relative to bilayer using cryogenic transmission electron microscopy (TEM). We demonstrate that antigen (OVA or HBsAg) formulated with SLA lipid adjuvants using all the different methodologies resulted in a strong antigen-specific immune response. Nevertheless, the advantage of using a drug substance process that comprises of simply admixing antigen with pre-formed empty archaeosomes, represents a simple, efficient and antigenic dose-sparing formulation for adjuvanting and delivering vaccine antigens.
类病毒体是由天然或合成的古菌脂质组成的脂质体，可用作佐剂，以诱导针对包封抗原的强烈持久的体液和细胞介导的免疫应答。然而，使用标准脂质体制备方法制备的类病毒体对包封抗原的包封效率通常仅为 5-40%。在这项研究中，我们使用一种简单的半合成古菌脂质（SLA，硫酸化乳酰基古菌醇）和两种不同的抗原（卵清蛋白（OVA）和乙型肝炎表面抗原（HBsAg））评估了不同的配方方法。使用常规的薄膜水化-再水化方法，在有或没有去除未包封抗原的情况下，或预先形成的空类病毒体与抗原溶液简单混合，将抗原包封在类病毒体中。确定了物理化学特性（粒径分布、Zeta 电位、囊泡形态和层状结构），以及使用低温透射电子显微镜（TEM）确定抗原相对于双层的位置。我们证明，使用 SLA 脂质佐剂通过所有不同方法学制备的抗原（OVA 或 HBsAg）可引发强烈的抗原特异性免疫应答。然而，使用包含简单混合抗原与预先形成的空类病毒体的药物制剂工艺的优势在于，对于佐剂和递送疫苗抗原而言，这是一种简单、高效且节省抗原剂量的制剂。
