Immunomodulatory chitosan nanoparticles for Toxoplasma gondii infection: Novel application of chitosan in complex propranolol-hydrochloride as an adjuvant in vaccine delivery

The study aimed to investigate the immunomodulatory effects of propranolol hydrochloride (PRO) in combination with chitosan nanoparticles (CS NPs) as an adjuvant to develop an effective vaccine against T. gondii. A total of 105 BALB/c mice were randomly divided into seven equal groups including PBS alone, CS NPs, SAG1 (Surface antigen 1), CS-SAG1 NPs, CS-PRO NPs, SAG1-PRO, and CS-SAG1-PRO NPs. The immunostimulatory effect of each adjuvant used for vaccine delivery was evaluated in a mice immunization model. The results showed that the mice immunized with CS-SAG1-PRO NPs exhibited the highest lymphocyte proliferation rate, along with increased secretion of IFN-gamma, TNF-alpha, IL-6, IL-12, IL-17, and IL-23, as well as elevated levels of protective cytokines such as TGF-beta, IL-27, and IL-10. Although, the CS-SAG1-PRO NPs immunized mice showed the highest level of T. gondii specific IgG compared to the other groups, a significant production of IgG2a and IgG1 was observed in the sera of mice immunized with the CS-SAG1-PRO NPs compared to the other group (p <0.001). The higher IgG2a/IgG1 ratio observed in the CS-SAG1-PRO NPs group indicates a bias towards Th1 cell polarization, suggesting the promotion of Th1 cell-mediated immune responses. Considering the combination of the highest lymphocyte proliferation and survival rates, IgG2a/IgG1 ratio, and cytokine levels in the mice immunized with CS-SAG1-PRO NPs, this approach holds promise for immunostimulation and vaccine delivery against T. gondii infection.