Enhancement of intranasal mucosal immunization of mucosal vaccines by ultrasonic treatment

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 (MnO 2 ) 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 MnO 2 @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, MnO 2 @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 MnO 2 @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. Graphic abstract