Vaccines are urgently needed to control the ongoing pandemic COVID-19 and previously emerging MERS/SARS caused by coronavirus (CoV) infections. The CoV spike receptor-binding domain (RBD) is an attractive vaccine target but is undermined by limited immunogenicity. We describe a dimeric form of MERS-CoV RBD that overcomes this limitation. The RBD-dimer significantly increased neutralizing antibody (NAb) titers compared to conventional monomeric form and protected mice against MERS-CoV infection. Crystal structure showed RBD-dimer fully exposed dual receptor-binding motifs, the major target for NAbs. Structure-guided design further yielded a stable version of RBD-dimer as a tandem repeat single-chain (RBD-sc-dimer) which retained the vaccine potency. We generalized this strategy to design vaccines against COVID-19 and SARS, achieving 10- to 100-fold enhancement of NAb titers. RBD-sc-dimers in pilot scale production yielded high yields, supporting their scalability for further clinical development. The framework of immunogen design can be universally applied to other beta-CoV vaccines to counter emerging threats. Display omitted •A dimeric form of MERS-CoV RBD is highly immunogenic and protective in mice•RBD-dimer structure guides further design of a homogeneous dimer by tandem repeat•The strategy is generalizable to design beta-CoV vaccines against COVID-19 and SARS•CoV RBD-dimer immunogens can be produced at high yields in pilot scale production Gao et al. present the structure-guided design of a coronavirus immunogen comprised of two protein subunits each containing the virus spike receptor binding domain fused together via a disulfide link or tandem repeat. The immunogen elicits strong immunogenicity in mice and protects them against viral challenge. The vaccine design strategy can be universally applied to SARS, MERS, COVID-19, and other CoV vaccines to counter emerging threats.