A new nanoparticle vaccine for SARS-CoV-2, the virus that causes COVID-19, has shown hints of protection and immunity in a preclinical study, safely eliciting the production of antibodies and antiviral T cell responses in mice and pigtail macaques. The vaccine generated robust immune responses with a single injection in mice - an important goal for vaccine researchers. Although more studies are needed to establish its protection, the vaccine represents a promising candidate for a badly needed, practical vaccine for COVID-19. To be successful in the field, any COVID-19 vaccine would need to protect people from disease after only one or two doses and would incorporate ingredients that can be easily manufactured and distributed. Here, Jesse Erasmus and colleagues formulated a vaccine for SARS-CoV-2 based on repRNAs, molecules that tend to generate stronger immune responses compared with the mRNAs used in more conventional vaccines. Their vaccine, named repRNA-CoV2S, includes repRNAs based on sequences from the SARS-CoV-2 spike protein - which allows the virus to enter human cells - alongside an emulsion of nanoparticles that enhance the vaccine's immunogenicity and stability. The authors saw that a single injection produced large amounts of antibodies against SARS-CoV-2 in mice and adding a booster injection heightened the vaccine's effects in older rodents and generated strong responses from T cells in the spleen and lungs. Both the single-shot and booster approaches were safe and produced similar responses in macaques that lasted for at least 70 days. Furthermore, antibodies from the macaques neutralized quantities of the SARS-CoV-2 virus similar to the concentrations observed in the serum of people recovering from infection. The authors note they plan to begin clinical development of the vaccine under the name HDT-301.