BackgroundAdjuvants use several mechanisms to boost immunogenicity and to modulate immune response. The strength of adsorption of antigen by adjuvants can be a determinant factor for significant improvement of immunopotentiation.MethodsWe expressed recombinant RBD‐FC in PichiaPink Strain 4 and examined the vaccination of mice by vaccine formulation with different adjuvants (sodium alginate and aluminum hydroxide, alone and together).ResultsSodium alginate significantly increased the immunogenicity and stability of RBD‐FC antigen, so RBD‐FC formulated with combined alginate and alum (AlSa) and sodium alginate alone showed higher antibody titer and stability. Immunogenicity of RBD‐FC:AlSa was determined by serological assays including direct enzyme‐linked immunosorbent assay (ELISA) and surrogate virus neutralization test (sVNT). High levels of IgGs and neutralizing antibodies were measured in serum of mice immunized with the RBD‐FC:AlSa formulation. On the other hand, cytokines IL‐10 and INF‐γ were severely accumulated in response to RBD‐FC:AlSa, and after 10 days, their accumulation was significantly declined, whereas IL‐4 showed the highest and the lowest accumulation in response to alum and alginate, respectively.ConclusionsOur data may suggest that combination of alum and sodium alginate has a better compatibility with RBD‐FC in vaccine formulation.