The emerging variants of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in pandemic call for the urgent development of universal corona virus disease 2019 (COVID-19) vaccines which could be effective for both wild-type SARS-CoV-2 and mutant strains. In the current study, we formulated protein subunit vaccines with AS03 adjuvant and recombinant proteins of S1 subunit of SARS-CoV-2 (S1-WT) and S1 variant (K417N, E484K, N501Y, and D614G) subunit (S1-Mut), and immunized transgenic mice that express human angiotensin-converting enzyme 2 (hACE2). The S1 protein-specific antibody production and the neutralization capability for SARS-CoV-2 and B.1.351 variant were measured after immunization in mice. The results revealed that the S1-Mut antigens were more effective in inhibiting the receptor-binding domain and ACE2 binding in B.1.351 variant than in wild-type SARS-CoV-2. Furthermore, the development of a bivalent vaccine exhibited the ideal neutralization properties against wild-type and B.1.351 variant, as well as other variants. Our findings may provide a rationale for the development of a bivalent recombinant vaccine targeting the S1 protein that can induce the neutralizing antibodies against both SARS-CoV-2 variants and wild-type of the virus and may be of importance to explore the potential clinical use of bivalent recombinant vaccine in the future.