2024/07/12 by Jacob Schön, G. Tuba Barut, Bettina Salome Trüeb +35 · 1 voice · 2 citations
Agricultural and Biological Sciences · Medicine · #Animal Virus Infections Studies #SARS-CoV-2 and COVID-19 Research #Viral gastroenteritis research and epidemiology
paper · pdf · doi:10.1038/s41564-024-01755-1
openalex publication_date 2024/07/12 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01
Approved vaccines are effective against severe COVID-19, but broader immunity is needed against new variants and transmission. Therefore, we developed genome-modified live-attenuated vaccines (LAV) by recoding the SARS-CoV-2 genome, including 'one-to-stop' (OTS) codons, disabling Nsp1 translational repression and removing ORF6, 7ab and 8 to boost host immune responses, as well as the spike polybasic cleavage site to optimize the safety profile. The resulting OTS-modified SARS-CoV-2 LAVs, designated as OTS-206 and OTS-228, are genetically stable and can be intranasally administered, while being adjustable and sustainable regarding the level of attenuation. OTS-228 exhibits an optimal safety profile in preclinical animal models, with no side effects or detectable transmission. A single-dose vaccination induces a sterilizing immunity in vivo against homologous WT SARS-CoV-2 challenge infection and a broad protection against Omicron BA.2, BA.5 and XBB.1.5, with reduced transmission. Finally, this promising LAV approach could be applicable to other emerging viruses.