OTS-228

OTS-228 (also known as RVX-OTS) is a next-generation, intranasal, live-attenuated vaccine (LAV) designed to prevent COVID-19 caused by SARS-CoV-2, including emerging variants such as Omicron BA.2, BA.5, and XBB.1.5. Developed by RocketVax in collaboration with the University of Bern, the Institute of Virology and Immunology (IVI), and the Friedrich-Loeffler-Institut, OTS-228 is engineered using a rational "One-to-Stop" (OTS) genome recoding strategy. This approach introduces synonymous codon changes that increase the likelihood of premature termination codons, thereby reducing viral fitness and ensuring stable attenuation. Additional modifications include disabling Nsp1-mediated translational repression, deleting open reading frames (ORFs) 6, 7ab, and 8 to enhance host immune responses, and optimizing the spike polybasic cleavage site to prevent reversion to virulence. In preclinical models, intranasal administration of OTS-228 demonstrated robust safety, high genomic stability, and sterilizing immunity, completely blocking transmission to contact animals.