Enhancement of the immunogenicity of a Mycobacterium tuberculosis fusion protein using ISCOMATRIX and PLUSCOM nano-adjuvants after nasal administration in mice

BACKGROUND AND OBJECTIVESTuberculosis (TB), a contagious disease caused by Mycobacterium tuberculosis (M. tuberculosis), remains a health problem worldwide and this infection has the highest mortality rate among bacterial infections. Current studies suggest that intranasal administration of new tuberculosis vaccines could enhance the immunogenicity of M. tuberculosis antigens. Hence, we aim to evaluate the protective efficacy and immunogenicity of HspX/EsxS fusion protein of M. tuberculosis along with ISCOMATRIX and PLUSCOM nano-adjuvants and MPLA through the intranasal administration in mice model.MATERIALS AND METHODSIn present study, the recombinant fusion protein was expressed in Escherichia coli and purified and used to prepare different nanoparticle formulations in combination with ISCOMATRIX and PLUSCOM nano-adjuvants and MPLA. Mice were intranasally vaccinated with each formulation three times at an interval of ۲ weeks. Three weeks after final vaccination, IFN-γ, IL-۴. IL-۱۷ and TGF-β concentration in supernatant of cultured splenocytes of vaccinated mice as well as serum titers of IgG۱ and IgG۲a and sIgA titers in nasal lavagewere determined.RESULTS AND DISCUSSIONAccording to obtained results, intranasally vaccinated mice with formulations containing ISCOMATRIX and PLUSCOM nano-adjuvants and MPLA could effectively induced IFN-γ and sIgA responses. Moreover, both HspX/EsxS/ISCOMATRIX/MPLA and HspX/EsxS/PLUSCOM/MPLA and their BCG booster formulation could strongly stimulate the immune system and enhance the immunogenicity of M. tuberculosis antigens.CONCLUSIONThe results demonstrate the potential of HspX/EsxS-fused protein in combination with ISCOMATRIX, PLUSCOM and MPLA after nasal administration in enhancing immune response against of M. tuberculosis antigens. Both nanoparticles were good adjuvants in order to promote immunogenicity of TB fused antigen. So, nasal immunization with these formulations, could induce immune responses and considered as new TB vaccine or as BCG booster.

کلیدواژه ها:

Mycobacterium tuberculosis ، HspX/EsxS ، ISCOMATRIX ، PLUSCOM ، MPLA ، Nasal administration.