Publication date: Aug 26, 2024
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) continues its significant health and economic impact globally. Despite the success of spike-protein vaccines in preventing severe disease, long-lasting protection against emerging variants and the prevention of breakthrough infections and transmission remain elusive. We generate an intranasal live-attenuated SARS-CoV-2 vaccine, CDO-7N-1, using codon deoptimization. CDO-7N-1 shows highly attenuated replication and minimal or no lung pathology in vivo over multiple passages. It induces robust mucosal and systemic neutralizing antibody and T-cell subset responses, in mice (female K18-hACE2 and male HFH4-hACE2 mice), hamsters, and macaques triggered by a single immunization. Mice and hamsters vaccinated with CDO-7N-1 are protected from challenge with wild-type (WT) SARS-CoV-2 and other variants of concern. Serum from vaccinated animals neutralizes WT SARS-CoV-2, variants of concern (beta and delta), variants of interest (omicron XBB. 1.5) and SARS-CoV-1. Antibody responses are sustained and enhanced by repeated immunization or infection with WT SARS-CoV-2. Immunity against all SARS-CoV-2 proteins by CDO-7N-1 should improve efficacy against future SARS-CoV-2 variants.
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Semantics
| Type | Source | Name |
|---|---|---|
| disease | VO | dose |
| disease | VO | vaccine |
| disease | VO | Severe acute respiratory syndrome coronavirus 2 |
| disease | MESH | COVID-19 |
| drug | DRUGBANK | Spinosad |
| disease | MESH | breakthrough infections |
| disease | IDO | replication |
| disease | IDO | cell |
| disease | VO | immunization |
| disease | VO | vaccinated |
| disease | MESH | infection |
| disease | MESH | Severe acute respiratory syndrome |
| pathway | KEGG | Viral replication |
| disease | VO | vaccination |
| disease | VO | effective |
| disease | VO | efficiency |
| disease | VO | Viruses |
| disease | VO | vaccine candidate |
| disease | VO | organ |
| drug | DRUGBANK | Coenzyme M |
| drug | DRUGBANK | Aminosalicylic Acid |
| drug | DRUGBANK | Dimercaprol |
| disease | MESH | pulmonary inflammation |
| drug | DRUGBANK | L-Arginine |
| disease | VO | immunized |
| disease | VO | gene |
| disease | VO | Glycoprotein |
| disease | IDO | homo sapiens |
| drug | DRUGBANK | L-Glutamine |
| drug | DRUGBANK | L-Isoleucine |
| drug | DRUGBANK | Proline |
| drug | DRUGBANK | L-Threonine |
| drug | DRUGBANK | L-Alanine |
| drug | DRUGBANK | Glycine |
| disease | VO | frequency |
| disease | IDO | assay |