Pharmacy laboratory, Department of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning, China.
Ji-Wen Zhang laboratory, Center for Drug Delivery System, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Pudong New Area, Shanghai, China.
Front Immunol. 2023 Feb 9;14:1132129. doi: 10.3389/fimmu.2023.1132129. eCollection 2023.
Mucosal immunization was an effective defender against pathogens. Nasal vaccines could activate both systemic and mucosal immunity to trigger protective immune responses. However, due to the weak immunogenicity of nasal vaccines and the lack of appropriate antigen carriers, very few nasal vaccines have been clinically approved for human use, which was a major barrier to the development of nasal vaccines. Plant-derived adjuvants are promising candidates for vaccine delivery systems due to their relatively safe immunogenic properties. In particular, the distinctive structure of pollen was beneficial to the stability and retention of antigen in the nasal mucosa.
Herein, a novel wild-type chrysanthemum sporopollenin vaccine delivery system loaded with a w/o/w emulsion containing squalane and protein antigen was fabricated. The unique internal cavities and the rigid external walls within the sporopollenin skeleton construction could preserve and stabilize the inner proteins. The external morphological characteristics were suitable for nasal mucosal administration with high adhesion and retention.
Secretory IgA antibodies in the nasal mucosa can be induced by the w/o/w emulsion with the chrysanthemum sporopollenin vaccine delivery system. Moreover, the nasal adjuvants produce a stronger humoral response (IgA and IgG) compared to squalene emulsion adjuvant. Mucosal adjuvant benefited primarily from prolongation of antigens in the nasal cavity, improvement of antigen penetration in the submucosa and promotion of CD8+ T cells in spleen.
Based on effective delivering both the adjuvant and the antigen, the increase of protein antigen stability and the realization of mucosal retention, the chrysanthemum sporopollenin vaccine delivery system has the potential to be a promising adjuvant platform. This work provide a novel idea for the fabrication of protein-mucosal delivery vaccine.
黏膜免疫是抵御病原体的有效防线。鼻腔疫苗能够激活全身和黏膜免疫，引发保护性免疫反应。然而，由于鼻腔疫苗的免疫原性较弱，以及缺乏合适的抗原载体，临床上仅有极少数鼻腔疫苗被批准用于人体，这是鼻腔疫苗发展的主要障碍。植物来源的佐剂因其具有相对安全的免疫原性而成为疫苗递送系统的有前途的候选物。特别是花粉独特的结构有利于抗原在鼻腔黏膜中的稳定性和保留。
本文构建了一种新型野菊花孢粉素疫苗递送系统，该系统负载了含有角鲨烷和蛋白质抗原的 w/o/w 乳液。孢粉素骨架结构内部的独特内腔和刚性外壁可以保存和稳定内部蛋白质。其外部形态特征适合鼻腔黏膜给药，具有高黏附性和保留性。
w/o/w 乳液与野菊花孢粉素疫苗递送系统可诱导鼻黏膜分泌型 IgA 抗体。此外，与角鲨烷乳液佐剂相比，鼻腔佐剂产生了更强的体液免疫反应（IgA 和 IgG）。黏膜佐剂主要受益于抗原在鼻腔中的延长停留时间、增强抗原在黏膜下的渗透以及促进脾脏中 CD8+T 细胞的增殖。
基于有效递呈佐剂和抗原、提高蛋白抗原稳定性以及实现黏膜保留的功能，野菊花孢粉素疫苗递送系统具有成为一种有前途的佐剂平台的潜力。这项工作为蛋白质黏膜递送疫苗的制备提供了新的思路。
