Reflecting the urgency to develop prophylactic approaches against COVID-19, several vaccine candidates have entered clinical trials before showing efficacy in animal models. In this preprint, Corbett et al. describe a preclinical study evaluating an mRNA vaccine candidate by Moderna. Immunization of mice with mRNA encoding stabilized prefusion SARS-CoV-2 spike trimers elicited dose-dependent neutralizing antibody and CD8+ T cell responses. Two doses given in prime–boost combination (2 x 1 µg/mouse) protected mice against infection of the nasal mucosa and lungs after challenge with mouse-adapted SARS-CoV-2. Importantly, there was no indication of enhanced immunopathology in animals that received sub-protective doses. A phase III efficacy trial in humans (using a single 100 µg dose regimen) is set to start in July.