Live attenuated SARS-CoV-2 vaccine candidate: Protective immunity without serious lung lesions in Syrian hamsters

Various COVID-19 vaccine candidates are currently under clinical trial. However, no live attenuated vaccine has been developed yet, despite their generally high efficacy. Here, we established temperature-sensitive mutant strains of SARS-CoV-2, whose growth was significantly slower than that of the parent strain at 37°C. One of the strains, A50-18, which presented mutations in nonstructural protein 14, did not replicate at all at 37°C in vitro . In vivo experiments demonstrated that this strain replicated inefficiently in the lungs of Syrian hamsters, and intra-nasal inoculation induced sufficient anti-SARS-CoV-2-neutralizing antibodies to protect against wild type virus infection. These results suggest that the A50-18 strain could be a promising live attenuated vaccine candidate against SARS-CoV-2. One Sentence Summary A live attenuated virus provided immunity against SARS-CoV-2 in an animal model, making it a promising vaccine candidate. ### Competing Interest Statement S.O., A.K., H.S., P.M., S.T., K.Y., and H.E. are employed by The Research Foundation for Microbial Diseases of Osaka University (BIKEN). We report that S.O., A.K., and H.E. are named on a patent that describes the use of the TS mutants as vaccines, currently being filed by BIKEN.