A novel antigen of Mycobacterium tuberculosis and MPLA adjuvant co-entrapped into PLGA:DDA hybrid nanoparticles stimulates mucosal and systemic immunity. (December 2018) - Khademi, Farzad
Abstract: Background: Due to initiation of Mycobacterium tuberculosis infection via the mucosal tissue of the respiratory tract, intranasal administration of new tuberculosis vaccines is highly regarded to enhance mucosal immunity. Our outline was evaluation of mucosal and systemic immune responses in BALB/c mice after nasal delivery of HspX/EsxS fused antigen of Mycobacterium tuberculosis along with MPLA adjuvant entrapped in PLGA:DDA hybrid nanoparticles. Methods: In this study, the double emulsion solvent evaporation method (w/o/w) was used to prepare different nanoparticle formulations containing HspX/EsxS protein and MPLA. Three weeks after the last nasal immunization of BALB/c mice, IgA antibody levels in nasal lavage and IFN-γ, IL-4, IL-17 and TGF-β cytokines in supernatant of cultured splenocytes and also serum IgG1 and IgG2a titers were evaluated using ELISA method. Results: Our results indicated that nasal vaccination with PLGA:DDA nanoparticles loaded with HspX/EsxS protein±MPLA, both with and without a prime dose of BCG could provide efficient Th1, Th17, IgA, IgG1 and IgG2a immune responses. Conclusion: These findings demonstrate that both PLGA:DDA hybrid nanoparticles as carrier/adjuvant and MPLA as adjuvant, could efficiently induce mucosal and systemic immune responses against HspX/EsxS antigen, alone or as a booster for BCG. Highlights: PLGA:DDA nanoparticle enhances immunogenicity of HspX/EsxS antigen of M. tuberculosis . MPLA adjuvant enhances immunogenicity of HspX/EsxS antigen of M. tuberculosis . Intranasal delivery of PLGA:DDA/HspX/EsxS/MPLA induces antigen-specific Th1, Th17 and IgA immune responses in animal models.