Numerous studies have demonstrated that targeting immunogens to Fc gamma R on antigen-presenting cells (APCs) can selectively uptake and increase cellular immunity in vitro and in vivo. Therefore, the present study was conducted to evaluate immunogenicity of a novel multistage tuberculosis vaccine, a combination of an early and a dormant immunogenic protein, ESAT6 and HspX, fused to Fc gamma 2a fragment of mouse IgG2a to target all forms of tuberculosis. Codon-optimized genes consisting of ESAT6, a linker, and HspX fused either to mouse Fc gamma 2a (ESAT6:HspX:mFc gamma 2a) or 6x His-tag (ESAT6:HspX:His) were synthesized. The resulting proteins were then produced in Pichia pastoris. The fusion proteins were separately emulsified in dimethyldioctadecylammonium bromide(DDA)-trehalose-6,6-dibehenate(TDB) adjuvant, and their immunogenicity with and without bacille Calmette-Gu,rin (BCG) was assessed in C57BL/6 mice. Th1, Th2, Th17, and T-reg cytokine patterns were evaluated using the ELISA method. Both multistage vaccines induced very strong IL-12 and IFN-gamma secretion from splenic cells; the Fc-tagged subunit vaccine induced a more effective Th1 immune response (IFN-gamma, 910 pg/mL, and IL-12, 854 pg/mL) with a very low increase in IL-17 (similar to 0.1 pg/mL) and IL-4 (37 pg/mL) and a mild increase in TGF-beta (543 pg/mL) compared to the BCG or ESAT6:HspX:His primed and boosted groups. The production of IFN-gamma to ESAT6:HspX:Fc gamma 2a was very consistent and showed an increasing trend for IL-12 compared to the BCG or ESAT6:HspX:His primed and boosted groups. Fc gamma 2a used as a delivery vehicle supported the idea of selective uptake, inducing cross-presentation and forming a proper anti-tuberculosis response in context of Th1/Th2 and Th17/T-reg balances, which is important for protection and prevention of damage.