Human Health Therapeutics Research Center, National Research Council Canada, Ottawa, ON, Canada.
Nanotechnology Research Center, National Research Council Canada, Edmonton, AB, Canada.
J Liposome Res. 2021 Sep;31(3):237-245. doi: 10.1080/08982104.2020.1786115. Epub 2020 Jul 23.
Archaeosomes, composed of sulphated lactosyl archaeol (SLA) glycolipids, have been proven to be an effective vaccine adjuvant in multiple preclinical models of infectious disease or cancer. In addition to efficacy, the stability of vaccine components including the adjuvant is an important parameter to consider when developing novel vaccine formulations. To properly evaluate the potential of SLA glycolipids to be used as vaccine adjuvants in a clinical setting, a comprehensive evaluation of their stability is required. Herein, we evaluated the long term stability of preformed empty SLA archaeosomes prior to admixing with antigen at 4 °C or 37 °C for up to 6 months. In addition, the stability of adjuvant and antigen was evaluated for up to 1 month following admixing. Multiple analytical parameters evaluating the molecular integrity of SLA and the liposomal profile were assessed. Following incubation at 4 °C or 37 °C, the SLA glycolipid did not show any pattern of degradation as determined by mass spectroscopy, nuclear magnetic resonance (NMR) and thin layer chromatography (TLC). In addition, SLA archaeosome vesicle characteristics, such as size, zeta potential, membrane fluidity and vesicular morphology, were largely consistent throughout the course of the study. Importantly, following storage for 6 months at both 4 °C and 37 °C, the adjuvant properties of empty SLA archaeosomes were unchanged, and following admixing with antigen, the immunogenicity of the vaccine formulations was also unchanged when stored at both 4 °C and 37 °C for up to 1 month. Overall this indicates that SLA archaeosomes are highly stable adjuvants that retain their activity over an extended period of time even when stored at high temperatures.
基于硫酸化乳糖基胞壁酰六肽（SLA）糖脂的 archaeosomes 已被证实是多种传染病或癌症的临床前模型中的有效疫苗佐剂。除了功效之外，佐剂等疫苗成分的稳定性也是开发新型疫苗制剂时需要考虑的一个重要参数。为了正确评估 SLA 糖脂在临床环境中用作疫苗佐剂的潜力，需要对其稳定性进行全面评估。在此，我们在 4°C 或 37°C 下与抗原混合前，评估了预先形成的空 SLA archaeosomes 的长期稳定性，最长可达 6 个月。此外，还评估了佐剂和抗原在混合后长达 1 个月的稳定性。评估了 SLA 和脂质体特征的多个分析参数，以评估 SLA 的分子完整性和脂质体的概况。在 4°C 或 37°C 孵育后，通过质谱、核磁共振（NMR）和薄层色谱（TLC）确定 SLA 糖脂没有任何降解模式。此外，SLA archaeosome 囊泡的特征，如大小、Zeta 电位、膜流动性和囊泡形态，在整个研究过程中基本保持一致。重要的是，在 4°C 和 37°C 下储存 6 个月后，空 SLA archaeosomes 的佐剂特性保持不变，并且在与抗原混合后，当在 4°C 和 37°C 下储存长达 1 个月时，疫苗制剂的免疫原性也保持不变。总的来说，这表明 SLA archaeosomes 是高度稳定的佐剂，即使在高温下储存，其活性也能保持很长时间。
