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AssigneeYale University
InventorsChen Liu, Lei Yang, John Rose
Estimating the term…
The present disclosure relates to the discovery of compositions and methods for therapeutic immunization for SARS-CoV-2 infections and/or disease(s) associated with expression of Glypican-3 (GPC3), including but not limited to cancers such as hepatocellular carcinoma (HCC). Methods of the disclosure include a method of generating virus like vesicles (VLVs), VLVs comprising SARS-CoV-2 antigens from a high titer VLV producing vector, VLVs comprising GPC3 antigens from a high titer VLV producing vector, methods of treating, ameliorating, and/or preventing SARS-COV-2 infection, methods of inducing a memory T and B cell immune response against SARS-CoV-2 infection in a, methods of treating, ameliorating, and/or preventing GPC3 associated disease, and methods of inducing a memory T and B cell immune response against GPC3 in a subject. Furthermore, the disclosure encompasses a pharmaceutical composition for vaccinating a subject to protect the subject against infection with
A virus like vesicle (VLV)-producing vector comprising a DNA sequence comprising a promoter sequence operably linked to a DNA sequence encoding Semliki Forest virus (SFV) non-structural protein nucleotide sequences, operably linked to an SFV subgenomic RNA promoter, operably linked to DNA encoding a SARS-CoV-2 antigen or fragment thereof, which is operably linked to a 2A DNA encoding a 2A peptide,
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A VLV producing vector comprising a DNA sequence comprising a promoter sequence operably linked to a DNA sequence encoding alphavirus non-structural protein nucleotide sequences, operably linked to an alphavirus subgenomic RNA promoter, operably linked to DNA encoding a SARS-CoV-antigen or fragment thereof, operably linked to a 2A DNA encoding a 2A peptide, which is in turn operably linked to a vesicular stomatitis virus (VSV) G DNA encoding a VSV G protein, wherein the alphavirus non-structural protein nucleotide sequences comprise at least two of the mutations selected from the group consisting of G-4700-A, A-5424-G, G-5434-A, T-5825-C, T-5930-C, A-6047-G, G-6783-A, G-6963-A, G-7834-A, T-8859-A, T-8864-C, G-9211-A, A-10427-G, G-11560-A, A-11871-G, and T-11978-C, wherein the vector lacks nucleotide sequences which encode alphavirus structural proteins, further wherein when the vector is propagated in cell culture, titers of at least 107 plaque forming units (pfu) per ml of virus like vesicles (VLVs) are obtained.
A virus like vesicle (VLV) producing vector comprising a DNA sequence comprising a promoter sequence operably linked to a DNA sequence encoding Semliki Forest virus (SFV) non-structural protein nucleotide sequences, operably linked to an SFV subgenomic RNA promoter, operably linked to DNA encoding a Glypican 3 (GPC3) protein or fragment thereof, operably linked to a 2A DNA encoding a 2A peptide, which is in turn operably linked to a vesicular stomatitis virus (VSV) G DNA encoding a VSV G protein, wherein the SFV non-structural protein nucleotide sequences comprise at least two of the mutations selected from the group consisting of G-4700-A, A-5424-G, G-5434-A, T-5825-C, T-5930-C, A-6047-G, G-6783-A, G-6963-A, G-7834-A, T-8859-A, T-8864-C, G-9211-A, A-10427-G, G-11560-A, A-11871-G, and T-11978-C, wherein the vector lacks nucleotide sequences which encode SFV structural proteins, further wherein when the vector is propagated in cell culture, titers of at least 107 plaque forming units (pfu) per ml of VLVs are obtained.
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A VLV producing vector comprising a DNA sequence comprising a promoter sequence operably linked to a DNA sequence encoding alphavirus non-structural protein nucleotide sequences, operably linked to an alphavirus subgenomic RNA promoter, operably linked to DNA encoding a GPC3 antigen or fragment thereof, operably linked to a 2A DNA encoding a 2A peptide, which is in turn operably linked to a vesicular stomatitis virus (VSV) G DNA encoding a VSV G protein, wherein the alphavirus non-structural protein nucleotide sequences comprise at least two of the mutations selected from the group consisting of G-4700-A, A-5424-G, G-5434-A, T-5825-C, T-5930-C, A-6047-G, G-6783-A, G-6963-A, G-7834-A, T-8859-A, T-8864-C, G-9211-A, A-10427-G, G-11560-A, A-11871-G, and T-11978-C, wherein the vector lacks nucleotide sequences which encode alphavirus structural proteins, further wherein when the vector is propagated in cell culture, titers of at least 107 plaque forming units (pfu) per ml of virus like vesicles (VLVs) are obtained.
Dependencies are inferred from the claim text.