Chiral Intranasal Nanovaccines as Antivirals for Respiratory Syncytial Virus

• Published in: Advanced materials (Weinheim) 2024-10, Vol.36 (41), p.e2408090
• Main Authors: Shi, Baimei, Qu, Aihua, Li, Zongda, Xiong, Yingcai, Ji, Jianjian, Xu, Liguang, Xu, Chuanlai, Sun, Maozhong, Kuang, Hua
• Format: Article
• Language: English
• Subjects: Epithelium; Nanoparticles; Proteins; Respiratory syncytial virus; Tumor necrosis factor-TNF
• ISSN: 0935-9648; 1521-4095; 1521-4095
• DOI: 10.1002/adma.202408090

This study aimed to develop an intranasal nanovaccine by combining chiral nanoparticles with the RSV pre-fusion protein (RSV protein) to create L-nanovaccine (L-Vac). The results showed that L-NPs increased antigen attachment in the nasal cavity by 3.83 times and prolonged its retention time to 72 h. In vivo experimental data demonstrated that the intranasal immunization with L-Vac induced a 4.86-fold increase in secretory immunoglobulin A (sIgA) secretion in the upper respiratory tract, a 1.85-fold increase in the lower respiratory tract, and a 20.61-fold increase in RSV-specific immunoglobin G (IgG) titer levels in serum, compared with the commercial Alum Vac, while the neutralizing activity against the RSV authentic virus is 1.66-fold higher. The mechanistic investigation revealed that L-Vac activated the tumor necrosis factor (TNF) signaling pathway in nasal epithelial cells (NECs), in turn increasing the expression levels of interleukin-6 (IL-6) and C-C motif chemokine ligand 20 (CCL20) by 1.67-fold and 3.46-fold, respectively, through the downstream nuclear factor kappa-B (NF-κB) signaling pathway. Meanwhile, CCL20 recruited dendritic cells (DCs) and L-Vac activated the Toll-like receptor signaling pathway in DCs, promoting IL-6 expression and DCs maturation, and boosted sIgA production and T-cell responses. The findings suggested that L- Vac may serve as a candidate for the development of intranasal medicine against various types of respiratory infections.