Publication date: Jul 12, 2024
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.
Open Access PDF
| Concepts | Keywords |
|---|---|
| Host | Attenuated |
| Sterilizing | Cov |
| Sustainable | Effective |
| Vaccine | Genome |
| Immunity | |
| Lav | |
| Live | |
| Modified | |
| Ots | |
| Profile | |
| Safety | |
| Sars | |
| Stop | |
| Transmission | |
| Vaccines |
Semantics
| Type | Source | Name |
|---|---|---|
| disease | VO | effective |
| disease | VO | vaccine |
| disease | MESH | COVID-19 |
| disease | MESH | repression |
| disease | IDO | host |
| disease | IDO | site |
| disease | VO | dose |
| disease | VO | vaccination |
| disease | MESH | infection |
| disease | VO | Viruses |
| disease | MESH | premature termination codons |
| disease | MESH | aids |
| disease | VO | efficiency |
| disease | VO | ORF68 |
| disease | MESH | weight loss |
| drug | DRUGBANK | Creatinolfosfate |
| drug | DRUGBANK | Indoleacetic acid |
| disease | IDO | virulence |
| disease | MESH | viral shedding |
| disease | IDO | replication |
| disease | MESH | genome stability |
| disease | VO | immunized |
| disease | VO | ReCOV |
| disease | VO | vaccinated |
| disease | VO | immunization |
| disease | MESH | breakthrough infections |
| disease | VO | viable |
| drug | DRUGBANK | Serine |
| drug | DRUGBANK | L-Leucine |
| pathway | KEGG | Viral replication |
| disease | IDO | susceptibility |
| drug | DRUGBANK | Fluorouracil |
| disease | MESH | pulmonary atelectasis |
| disease | MESH | morbidity |
| drug | DRUGBANK | Dimethyl sulfoxide |
| disease | VO | ORF |
| disease | VO | ANOVA |