Nasal immunization of mice with Esat-6 -loaded N-trimethyl chitosan nanoparticles induce high cellular immune response against tuberculosis

Background: The majority of pathogens, such as Mycobacterium tuberculosis, initiate infection by interacting with host mucosa. Owing to its great potential to increase immune response, chitosan can be considered as a suitable biodegradable polymer for intranasal administration. The purpose of this study was to demonstrate whether intranasal administration of ESAT-6 in TMC can promote and build up its inherent low immunogenicity Methods: Chitosan nanoparticles consist of ESAT-6 antigen prepared by ionic gelation method. The physiochemical properties of the nanoparticles, including morphology, particle size, zeta potential, encapsulation and antigen release profile were measured in vitro. Flowing three times of nasal immunization of BALB/C mice with ESAT-6 antigen in nanoparticles or soluble forms, serum level of specific antibody was measured by indirect Elisa. Two weeks after last immunization the levels of IFN-γ and IL-10 released from cultured lymphocyte were investigated. Results: After three times of nasal immunization, strong response of IFN-gamma and IL-4 were detected in nanoparticles immunized group. Moreover, this group shows a greater titer of specific IgG antibody in compare to ESAT-6 alone. Conclusion: These results demonstrated that chitosan nanoparticles could be considered as an effective vaccine delivery system to induce more appropriate immune responses against low inherent immunogenic tuberculosis proteins through intranasal routs.

Keywords:

TMC , nanoparticles , M. tuberculosis , ESAT-6