State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, PR China.
State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, PR China; University of Chinese Academy of Sciences, Beijing 100049, PR China.
Int J Pharm. 2022 Sep 25;625:122083. doi: 10.1016/j.ijpharm.2022.122083. Epub 2022 Aug 5.
Maintaining structural integrity and enhancing stability of inactivated foot-and-mouth disease virus (iFMDV) antigen in adjuvants is crucial to ensure the vaccine potency. Unfortunately, formulation with most reported adjuvants leads to the accelerated dissociation of iFMDV into inactive pentamers. Here, an ionic liquid, i.e., choline and niacin ([Cho][Nic]), which was found to stabilize iFMDV against the acid- and thermo- induced dissociation in buffer solution, was applied to construct a novel oil-in-ionic liquid (o/IL) nanoemulsion adjuvant composed of [Cho][Nic], squalene, and Tween 80. The o/IL nanoemulsion formulated with iFMDV has a monodisperse diameter of 135.8 ± 40.4 nm. The thermostability and long-term stability of iFMDV were remarkably enhanced in o/IL nanoemulsion compared with that in the o/w emulsion without [Cho][Nic] and in the commercial Montanide ISA 206 adjuvant. The o/IL nanoemulsion exerted its adjuvant effects by improving the humoral immune responses. Immunization of o/IL nanoemulsion adjuvanted iFMDV induced specific IgG titers similar to that adjuvanted by Montanide ISA 206 and about 4-fold higher than the un-adjuvanted iFMDV, also promoted the activation of B lymphocytes and the secretion of interleukin-4 in the mice model. This [Cho][Nic]-based o/IL nanoemulsion can serve as a promising adjuvant platform for the foot-and-mouth disease vaccine.
保持灭活口蹄疫病毒(iFMDV)抗原在佐剂中的结构完整性和增强稳定性对于确保疫苗效力至关重要。不幸的是,大多数报道的佐剂的配方会导致 iFMDV 加速解离为无活性的五聚体。在这里,我们发现一种离子液体,即胆碱和烟酸([Cho][Nic]),可以在缓冲溶液中稳定 iFMDV 免受酸和热诱导的解离,将其应用于构建一种由[Cho][Nic]、角鲨烯和 Tween 80 组成的新型油包离子液体(o/IL)纳米乳佐剂。用 iFMDV 配制的 o/IL 纳米乳粒径均匀,直径为 135.8±40.4nm。与不含[Cho][Nic]的 o/w 乳液和商业 Montanide ISA 206 佐剂相比,o/IL 纳米乳显著提高了 iFMDV 的热稳定性和长期稳定性。o/IL 纳米乳通过改善体液免疫反应发挥其佐剂作用。o/IL 纳米乳佐剂 iFMDV 的免疫接种诱导的特异性 IgG 滴度与 Montanide ISA 206 佐剂相当,比未佐剂的 iFMDV 高约 4 倍,还促进了 B 淋巴细胞的活化和白细胞介素-4 的分泌。这种基于[Cho][Nic]的 o/IL 纳米乳可以作为口蹄疫疫苗的一种有前途的佐剂平台。