Chitosan (CHT) and trimethylchitosan (TMC) nanoparticles as adjuvant/delivery system for parenteral and nasal immunization against Mycobacterium tuberculosis (MTb) ESAT-6 antigen

Objective(s): An efficient vaccine against TB is an urgent need. TB peptides are safe candidate but they are weak immunogens and needs to be potentiated by adjuvant/delivery systems. The main purpose of the present study was to determine the potential of CHT based NPs containing ESAT-6 antigen of M. tuberculosis for inducing mucosal and systemic immune responses after intranasal and subcutaneous injection in mice model. Materials and Methods: CHT and TMC based NPs were prepared by coating of cationic polymer on the anionic peptide by ionic gelation method and their characteristics were evaluated by scanning electron microscopy (SEM) and dynamic light scattering (DLS). Physical stability of NPs was studied within 30 days. Finally, the ability of formulated NPs to elicit immune responses in BALB/c mice were evaluated following nasal and subcutaneous immunization. Results: The best weight ratio of antigen to polymer (CHT or TMC) was 1:2. CHT and TMC NPs had a mean size of 356.3 ± 42.20, and 470.3 ± 48.21 nm, respectively. NPs were stable up to 15 days. CHT:ESAT-6 NPs gave higher serum IgG1 and IgG total responses and TMC:ESAT-6 NPs induced high titers of IgG2a and IFN-g. Conclusion: Regards to the importance of cellular immune responses in effective protection against TB, and also the solubility in physiological pH, TMC NPs are more efficient adjuvant/antigen delivery system for immunization against TB.

Keywords:

Chitosan and Trimethylchitosan nanoparticles , ESAT-6 antigen , Mycobacterium tuberculosis , Nasal immunization , Subcutaneous immunization