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The coronavirus disease 2019 (COVID‐19) pandemic posed great impacts on public health. To fight against the pandemic, robust immune responses induced by vaccination are indispensable. Previously, we developed a subunit vaccine adjuvanted by aluminum hydroxide, ZF2001, based on the dimeric tandem‐repeat RBD immunogen, which has been approved for clinical use. This dimeric RBD design was also explored as an mRNA vaccine. Both showed potent immunogenicity. In this study, a DNA vaccine candidate encoding RBD‐dimer was designed. The humoral and cellular immune responses induced by homologous and heterologous prime‐boost approaches with DNA‐RBD‐dimer and ZF2001 were assessed in mice. Protection efficacy was studied by the SARS‐CoV‐2 challenge. We found that the DNA‐RBD‐dimer vaccine was robustly immunogenic. Priming with DNA‐RBD‐dimer followed by ZF2001 boosting induced higher levels of neutralizing antibodies than homologous vaccination with either DNA‐RBD‐dimer or ZF2001, elicited polyfunctional cellular immunity with a TH1‐biased polarization, and efficiently protected mice against SARS‐CoV‐2 infection in the lung. This study demonstrated the robust and protective immune responses induced by the DNA‐RBD‐dimer candidate and provided a heterologous prime‐boost approach with DNA‐RBD‐dimer and ZF2001. [ABSTRACT FROM AUTHOR]