A Novel Intranasal Nano-Adjuvanted Pertussis Vaccine with Enhanced Mucosal Delivery and Immunogenicity in a Rodent Model

Abstract

The present study developed a novel nano-structured nasal Bordetella pertussis vaccine candidate using filamentous haemagglutinin (FHA) and pertussis toxoid (PTd) encapsulated in N-trimethyl chitosan (TMC) with cytosine phosphoguanine (CpG) serving as both an adjuvant and crosslinker (CpG-adjuvanted TMC/PTd-FHA), followed by physicochemical characterization and immune response evaluation after nasal administration. The TMC/CpG/PTd-FHA nanoparticle (NP) exhibited a particle size and zeta potential of 289.4 nm and +25.7 mV, respectively. The antigen/toxoid-loaded NPs exhibited encapsulation efficacy exceeding 80% in polymer matrices, whereas in vitro antigen/toxoid release was found to be 95.18% after 96 hours. High immunization rates were observed in NP-treated mice with increased IgG and secretory IgA levels and strong ability to induce IFN-γ, IL-4, and IL-17 compared with the control group. Overall, nasal administration of the proposed approach, utilizing CpG as an adjuvant and crosslinker, was able to elicit humoral and Th1-type cellular immune responses, demonstrating promising potential as a vaccine delivery system.