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Bio-Design and Manufacturing  2023 Vol.6 No.4 P.405-422

http://doi.org/10.1007/s42242-023-00231-9


Enhancement of intranasal mucosal immunization of mucosal vaccines by ultrasonic treatment


Author(s):  Haowei Xu, Yang Liao, Mankovskaya Svetlana, Deguang Yang, Huaibin Wan & Zonghua Liu

Affiliation(s):  Department of Biomedical Engineering, Jinan University, Guangzhou 510632, China; more

Corresponding email(s):   docvanhb@outlook.com, tliuzonghua@jnu.edu.cn

Key Words:  Mucosal vaccine, Ultrasound treatment, MnO2, Nasal delivery


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Haowei Xu, Yang Liao, Mankovskaya Svetlana, Deguang Yang, Huaibin Wan & Zonghua Liu. Enhancement of intranasal mucosal immunization of mucosal vaccines by ultrasonic treatment[J]. Journal of Zhejiang University Science D, 2023, 6(4): 405-422.

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Abstract: 
The pathogens of most infectious diseases invade the host through mucosal sites, and immunization with mucosal vaccines is the best means of combating these infectious diseases. Oral delivery and nasal delivery are the most common methods of mucosal vaccination. However, the delivery process is inefficient, and mucosal vaccination is ineffective because the vaccine formulation is easily and rapidly removed and has difficulty in crossing the mucosal surface. In this paper, we investigated whether the mucosal immune response could be enhanced by ultrasound facilitation of nasal mucosal delivery of vaccine preparations. For this purpose, we used manganese dioxide (mnO2) as the vaccine carrier/adjuvant, coated with chitosan oligosaccharide (COS) to enhance mucosal adsorption, and further physically adsorbed model antigen ovalbumin (OVA) to construct a nanoparticulate vaccine formulation mnO2@COS@OVA. ultrasound treatment was found to promote antigen delivery and recruitment of dendritic cells (DCs) and macrophages as well as T-cell infiltration in nasal mucosal tissues through nasal mucosal immunization studies. With ultrasound assistance, mnO2@COS@OVA particles promoted the maturation of DCs in vitro and in vivo and promoted the production of effector memory T cells in vivo and cytokine secretion by splenocytes in vitro. In particular, ultrasound treatment significantly increased the levels of secretory IgA antibodies in the nasal mucosa and genital tract mucosa of experimental mice. In addition, the experimental data showed that the mnO2@COS@OVA particles had good biocompatibility and caused no significant damage to the nasal mucosal and vital organ tissue. These data suggest that ultrasound treatment can promote the induction of efficient immune responses to mucosal vaccines and provide new ideas for the opening and clinical translation of mucosal vaccines.

暨南大学刘宗华团队 | 超声促进MnO₂疫苗制剂诱导鼻粘膜免疫应答

本研究论文聚焦于超声波辅助增强疫苗制剂的粘膜免疫递送。如今,大多数传染病的病原体通过粘膜部位侵入宿主,而粘膜疫苗的免疫接种是防治这些传染病的最佳手段。粘膜疫苗的接种方式,以口服递送与鼻腔递送最常见。然而,在递送过程中,由于疫苗制剂易被快速清除、难以穿过粘膜表层等原因,而导致递送效率低下,粘膜疫苗接种效果不佳。本文中,我们探究了是否可通过超声促进疫苗制剂的鼻粘膜递送而增强粘膜免疫应答。为此,我们以MnO2为疫苗载体/佐剂,在其表面涂覆COS以增强粘膜吸附性,进一步物理吸附模型抗原—OVA,构建成纳米颗粒状疫苗制剂MnO2@COS@OVA。通过鼻粘膜免疫接种研究发现,超声处理可促进抗原递呈和鼻粘膜组织中DCs与巨噬细胞的募集以及T细胞浸润。在超声辅助下,MnO2@COS@OVA颗粒可促进体内外DCs成熟,并促进体内效应记忆 T 细胞的产生,促进体外脾细胞分泌细胞因子。超声处理显著提高了实验鼠鼻粘膜与生殖道粘膜分泌型IgA抗体水平。此外,实验数据表明,MnO2@COS@OVA颗粒具有良好的生物相容性,对鼻粘膜组织与体内重要器官未造成明显损伤。这些数据表明,超声处理可促进粘膜疫苗诱导高效免疫应答,为粘膜疫苗开放与临床转化提供新思路。

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