Feasibility of chitosan-based nanoparticles approach for intranasal immunisation of live attenuated Japanese encephalitis vaccine.

Intranasal (IN) administration, a non-invasive route, is explored to overcome the limitations of conventional subcutaneous (SC) injection for Japanese encephalitis (JE) immunisation. Mucoadhesive nanoparticles (NPs) are recognised for the benefits they offer via IN delivery, such as extended retention time of the vaccine on the mucosa. The purpose of this study was to evaluate immunisation effect of live attenuated Japanese encephalitis-chimeric virus vaccine (JE-CV)-loaded mucoadhesive NPs based on chitosan (CS) or chitosan maleimide (CM), a novel mucoadhesive polymer, via the IN route to improve the mucosal immunisation against JE. The results revealed that IN immunisation stimulated seroprotection following PRNT50 evaluation. Moreover, compared with SC immunisation, IN immunisation in mice provided a higher sIgA level, leading to improved mucosal immune response. In addition, chitosan-based NPs showed an adjuvant effect on the IN vaccine due to their mucoadhesive and antigen-uptaken properties. CM NPs successfully induced sIgA. In contrast, SC JE-CV immunisation induced negligible mucosal immunity. These immunological advantages revealed that JE-CV-loaded mucoadhesive NPs are a promising approach for IN vaccination as an alternative route for JE protection due to the stimulatory effects on both mucosal and systemic immune responses.