Severe acute respiratory syndrome (SARS) is an emerging infectious disease caused by a new coronavirus (SARS-CoV). Recent studies suggest that SARS-CoV is zoonotic and may have a broad host range besides humans. Although the global outbreak of SARS has been contained, there are serious concerns over its re-emergence and bioterrorism potential. As a part of preparedness, development of a safe and effective vaccine is one of the highest priorities in fighting SARS. A number of candidate vaccines, using a variety of approaches, are under development. The first vaccine tested in clinical trial is made from the inactivated form of SARS-CoV. Several live attenuated, genetically engineered or vector vaccines encoding the SARS-CoV spike (S) protein have been in pre-clinical studies. These vaccine candidates are effective in terms of eliciting protective immunity in the vaccinated animals. However, caution should be taken with the safety of whole virus or full-length S protein-based immunogens in humans because they may induce harmful immune or inflammatory responses. We propose to use the receptor-binding domain (RBD) of SARS-CoV S protein (residues 318--510) for developing a safe and effective subunit SARS vaccine, as it is not only a functional domain that mediates virus-receptor binding but also a major neutralization determinant of SARSCoV. It has been demonstrated that the RBD of SARS-CoV S protein contains multiple conformational epitopes capable of inducing highly potent neutralizing antibody responses and protective immunity.