The live-attenuated yellow fever 17D (YF17D) vaccine was employed as a vector to express the profusion form of the SARS-CoV-2 Spike antigen. The vaccine candidate, tentatively named YF-S0, induces high levels of SARS-CoV-2 neutralizing antibodies and a favorable Th1 cell-mediated immune response in mice. In a stringent hamster SARS-CoV-2 challenge model, vaccine candidate YF-S0 prevents infection with SARS-CoV-2. Moreover, a single dose confers protection from lung disease in most vaccinated animals even within 10 days. These results warrant further development of YF-S0 as a potent SARS-CoV-2 vaccine candidate.