Pathogen‐Mimicking Nanoparticles Based on Rigid Nanomaterials as an Efficient Subunit Vaccine Delivery System for Intranasal Immunization

Author:

Wan Hongping12ORCID,Deng Kai12,Huang Zhengqun12,Yang Yunhan12,Jing Bo2,Feng Yumei3,Li Yuanfeng45,Liu Yong4,Lu Mingqin6,Zhao Xinghong127ORCID

Affiliation:

1. Center for Infectious Diseases Control (CIDC) Sichuan Agricultural University Chengdu 611130 China

2. Key Laboratory of Animal Disease and Human Health of Sichuan Province Sichuan Agricultural University Chengdu 611130 China

3. State Key Laboratory of Crop Gene Exploration and Utilization in Southwest China Sichuan Agricultural University at Wenjiang Chengdu 611130 China

4. Wenzhou Institute University of Chinese Academy of Sciences Wenzhou 325001 China

5. Translational Medicine Laboratory The First Affiliated Hospital of Wenzhou Medical University Wenzhou 325035 China

6. Department of Infectious Diseases The First Affiliated Hospital of Wenzhou Medical University Wenzhou 325035 China

7. Center for Sustainable Antimicrobials Department of Pharmacy Sichuan Agricultural University Chengdu 611130 China

Abstract

AbstractDespite the safety profile of subunit vaccines, the inferior immunogenicity hinders their application in the nasal cavity. This study introduces a novel antigen delivery and adjuvant system utilizing mucoadhesive chitosan–catechol (Chic) on silica spiky nanoparticles (Ssp) to enhance immunity through multiple mechanisms. The Chic functionalizes the Ssp surface and incorporates with SARS‐CoV‐2 spike protein receptor‐binding domain (RBD) and toll‐like receptor (TLR)9 agonist unmethylated cytosine‐guanine (CpG) motif, forming uniform virus‐like nanoparticles (Ssp‐Chic‐RBD‐CpG) via electrostatic and covalent interactions. Ssp‐Chic‐RBD‐CpG, mimicking the morphology and function of inactive virions, effectively prolongs the retention time of RBD in the nasal mucosa by 3.92‐fold compared to RBD alone, enhances the maturation of dendritic cells (DCs), and facilitates the antigen trafficking to the draining lymph nodes, which subsequently induces a stronger mucosal immunity. Mechanistically, the enhanced chemokine chemokine (C‐C motif) ligand 20 (CCL20)‐driven DCs recruitment and maturation by Ssp‐Chic‐RBD‐CpG are evidenced by a cell co‐culture model. In addition, the overexpression of TLR4/9 and activation of MYD88/NF‐κB signaling pathway in activation of DCs are observed. Proof of principle is obtained for RBD, but similar delivery mechanisms can be applied in other protein‐based subunit vaccines as well when intranasal administration is needed.

Funder

Sichuan Province Science and Technology Support Program

National Natural Science Foundation of China

1000 Talents Sichuan Program

Publisher

Wiley

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