A Live Attenuated Sars-Cov-2 and a Vaccine Made Thereof

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This invention describes a genetically modified live attenuated SARS-CoV-2 virus, designed as a safer, more effective vaccine against COVID-19. The virus is engineered using codon-pair deoptimization and the removal of the furin cleavage site in the spike protein gene, which reduces its ability to cause disease and to be transmitted between individuals but maintains its capacity to generate a strong and broad immune response. The approach targets a wide range of SARS-CoV-2 variants, including highly transmissible and immune-evasive ones like Delta and Omicron.

Use CasesContent extracted from patent full text and abstract with AI.

• Human vaccination against COVID-19 to prevent infection and transmission, especially using intranasal or oral administration.
• Booster vaccinations for improved mucosal and systemic immunity against emerging variants of SARS-CoV-2.
• Vaccination of immunosuppressed individuals, including those receiving glucocorticoid treatment, due to the enhanced safety profile.
• Animal vaccination for pets, laboratory animals, or potentially wildlife to reduce zoonotic transmission.
• Manufacture of pharmaceutical compositions (vaccines) based on this live attenuated virus for global immunization campaigns.

BenefitsContent extracted from patent full text and abstract with AI.

• Provides robust mucosal and systemic immunity, including strong neutralizing antibody and T-cell responses at the site of viral entry.
• Significantly reduces or blocks transmission of SARS-CoV-2, including highly infectious variants, thereby helping to control outbreaks.
• Enhanced safety features: attenuation via two independent mechanisms (codon-pair deoptimization and deletion of the furin cleavage site) minimize risk of disease and unwanted vaccine transmission.
• Genetic modifications prevent reversion to virulence and reduce the risk of recombination with circulating viruses.
• Increases yield and genetic stability in standard cell lines (e.g., Vero cells) used for vaccine manufacturing, reducing production costs.
• Broad cross-variant protection, potentially reducing the need for frequent vaccine updates as viruses evolve.
• Particularly well-suited for intranasal or oral administration, enabling easier, non-invasive mass immunization and inducing superior mucosal immunity.
• Demonstrated efficacy and safety in animal models, including immunocompromised hosts.

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Inventors & Applicants

Patent Abstract

The invention relates to a polynucleotide encoding a) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein; and/or b) at least one non-structural SARS-CoV-2 protein selected from the group consisting of non-structural protein 7, non-structural protein 8, non-structural protein 9, non-structural protein 10, non-structural protein 11, non-structural protein 12, an endoribonuclease, and a 2'-O-methyltransferase, wherein the polynucleotide comprises or consists of at least one sequence part comprising codon-pair deoptimizations in comparison to the SARS-CoV-2 genome, and wherein the polynucleotide further comprises a furin cleavage site modification resulting in a loss of a furin cleavage site being naturally present in the SARS-CoV-2 genome. The invention further relates to a live attenuated SARS- CoV-2 comprising this polynucleotide, to a vaccine comprising this live attenuated SARS-CoV-2, as well as to associated methods.