Background: Application of adjuvants with microbial origins is a recently highlighted approach in the vaccinology trials. Archaeosomes are among these microbial compounds with both adjuvant and liposomal activities and features. Methods: In the present study, recombinant HBsAg encapsulated into Methanobrevibacter smithii (M. smithii) archaeosomes. Balb/c mice immunized with this compound and humoral and cytokine secretion pattern of immunized models analyzed. Results: Frequency of IFN-γ secreting cells in the HBsAg-containing archaeosomes group was significantly higher than HBsAg and HBsAg+C/IFA groups (p≤0.05). IgG2a titer in the sera of HBsAg-containing archaeosomes group was also significantly higher than this subclass titer in the other groups (p≤0.05). Conclusion: Analysis of induced responses revealed the Immunopotentiating characteristics of M. smithii archaeosomes in the induction of T-helper 1 responses according to the dominance of IgG2a subtype and IFN-γ secreting splenocytes of immunized mice.