Martin Luther University Halle-Wittenberg, Institute of Pharmacy, Wolfgang-Langenbeck-Str. 4, 06120 Halle/Saale, Germany.
Martin Luther University Halle-Wittenberg, Institute for Biochemistry and Biotechnology, Kurt-Mothes-Straße 3, 06110 Halle/Saale, Germany.
Vaccine. 2018 Apr 19;36(17):2314-2320. doi: 10.1016/j.vaccine.2018.03.019. Epub 2018 Mar 19.
Potent adjuvant systems are required for subunit and single antigen based vaccines to provide sufficient immunogenicity. Furthermore, adjuvants can reduce the required number of immunisations and the antigen amount. Squalene nanoemulsions, like MF59® and AddaVax™, are potent, safe and well characterised adjuvant systems and approved for use in humans. Here, we developed squalene containing solid lipid nanoparticles, which can be sterilised by steam sterilisation and stored as freeze-dried power together with a yeast-based vaccine. Detailed size measurements using dynamic and static light scattering were applied, as the immune stimulating effect of squalene emulsions is mainly dependent on the particle size. The size range of AddaVax™ (120-170 nm) was favoured for the developed squalene containing solid lipid nanoparticles. Differential scanning calorimetry (DSC) and H NMR studies were performed to characterise the interactions of the incorporated liquid squalene with the solid hard fat matrix. A homogeneous distribution as liquid domains in the solid glyceride structure was suggested for the liquid squalene. The developed adjuvant was compared with Freund's adjuvant and a commercially available squalene nanoemulsion in a vaccine trial in the mouse model with a yeast-based vaccine directed against the infectious bursal disease virus. All squalene-based adjuvants showed excellent biocompatibility and provided immune stimulating properties comparable to Freund's adjuvant.
为了使亚单位疫苗和单价疫苗具有足够的免疫原性,需要使用有效的佐剂系统。此外,佐剂还可以减少免疫接种的次数和抗原用量。角鲨烯纳米乳,如 MF59® 和 AddaVax™,是有效的、安全的、特性良好的佐剂系统,已被批准用于人类。在这里,我们开发了含有角鲨烯的固体脂质纳米粒,可通过蒸汽灭菌进行消毒,并与基于酵母的疫苗一起冻干储存。详细的尺寸测量使用动态和静态光散射进行,因为角鲨烯乳剂的免疫刺激作用主要取决于粒径。开发的含有角鲨烯的固体脂质纳米粒优选 AddaVax™(120-170nm)的粒径范围。通过差示扫描量热法(DSC)和 H NMR 研究来表征掺入的液体角鲨烯与固体硬脂酸基质的相互作用。液体角鲨烯在固体甘油酯结构中呈现出均匀分布的液体域。在针对传染性法氏囊病病毒的酵母疫苗的小鼠模型中,将开发的佐剂与弗氏佐剂和市售的角鲨烯纳米乳进行了疫苗试验比较。所有基于角鲨烯的佐剂均表现出良好的生物相容性,并提供了与弗氏佐剂相当的免疫刺激特性。
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