Chiral Intranasal Nanovaccines as Antivirals for Respiratory Syncytial Virus

Abstract 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.