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壳聚糖基乳剂的制备作为增强鼻腔黏膜免疫应答的佐剂。

Fabrication of chitosan-based emulsion as an adjuvant to enhance nasal mucosal immune responses.

机构信息

College of Food Science and Technology, Huazhong Agricultural University, Wuhan 430070, China.

Hubei Gedian Humanwell Pharmaceutical Excipients Co., Ltd., Wuhan 430070, China.

出版信息

Int J Biol Macromol. 2024 Jun;272(Pt 2):132913. doi: 10.1016/j.ijbiomac.2024.132913. Epub 2024 Jun 6.

Abstract

Nasal vaccine is a non-invasive vaccine that activates systemic and mucosal immunity in the presence of an adjuvant, thereby enhancing immune function. In this work, chitosan/oligochitosan/tween 80 (CS-COS-T80) co-stabilized emulsion was designed and further used as the nasal adjuvant. CS-COS-T80 emulsion exhibited outstanding stability under pH 6-8 with uniformly dispersed droplets and nano-scale particle size (<0.25 μm), and maintained stable at 4 °C for 150-day storage. Addition of model antigen ovalbumin (OVA) had no effect on the stability of CS-COS-T80 emulsion. In vivo nasal immunity indicated that CS-COS-T80 emulsion prolonged the retention time of OVA in the nasal cavity (from 4 to 8 h to >12 h), as compared to T80-emulsion. CS-COS-T80 emulsion produced a stronger mucosal immune response to OVA, with secretory IgA levels 5-fold and 2-fold higher than those of bare OVA and commercial adjuvant MF59, respectively. Compared to MF59, CS-COS-T80 induced a stronger humoral immune response and a mixed Th1/Th2 immune response of OVA after immunization. Furthermore, in the presence of CS-COS-T80 emulsion, the secretion of IL-4 and IFN-γ and the activation of splenocyte memory T-cell differentiation increased from 173.98 to 210.21 pg/mL and from 75.46 to 104.01 pg/mL, respectively. Therefore, CS-COS-T80 emulsion may serve as a promising adjuvant platform.

摘要

鼻腔疫苗是一种非侵入性疫苗,在佐剂存在的情况下激活全身和黏膜免疫,从而增强免疫功能。在这项工作中,设计了壳聚糖/低聚壳聚糖/吐温 80(CS-COS-T80)共稳定乳液,并进一步将其用作鼻腔佐剂。CS-COS-T80 乳液在 pH 6-8 下表现出出色的稳定性,具有均匀分散的液滴和纳米级粒径(<0.25μm),并且在 4°C 下稳定储存 150 天。添加模型抗原卵清蛋白(OVA)对 CS-COS-T80 乳液的稳定性没有影响。体内鼻腔免疫表明,CS-COS-T80 乳液延长了 OVA 在鼻腔中的保留时间(从 4 小时延长至 8 小时以上),而 T80 乳液则没有。CS-COS-T80 乳液对 OVA 产生了更强的黏膜免疫反应,分泌型 IgA 水平分别比裸 OVA 和商业佐剂 MF59 高 5 倍和 2 倍。与 MF59 相比,CS-COS-T80 在免疫后诱导了更强的体液免疫反应和 OVA 的混合 Th1/Th2 免疫反应。此外,在 CS-COS-T80 乳液存在的情况下,IL-4 和 IFN-γ 的分泌以及脾细胞记忆 T 细胞分化的激活分别从 173.98 增加到 210.21pg/mL 和从 75.46 增加到 104.01pg/mL。因此,CS-COS-T80 乳液可能成为一种有前途的佐剂平台。

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