Modified alphavirus vectors
AssigneeGritstone Bio, Inc.
InventorSue-Jean Hong
Life of this patent
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Abstract
Disclosed herein are vaccine compositions that include alphavirus derived vectors having multiple expression cassettes driven by multiple subgenomic promoters.
Claims46
A composition for delivery of an antigen expression system comprising a self-replicating alphavirus-based expression system, wherein the composition for delivery of the self-replicating alphavirus-based expression system comprises:
- the self-replicating alphavirus-based expression system, wherein the self-replicating alphavirus-based expression system comprises one or more vectors, wherein the one or more vectors comprise:
- (a) an RNA alphavirus backbone, wherein the RNA alphavirus backbone comprises:
- (i) at least one promoter nucleotide sequence, and
- (ii) at least one polyadenylation (poly(A)) sequence;
- and
- (b) at least two cassettes, wherein each of the cassettes independently comprise:
- (i) at least one antigen-encoding nucleic acid sequence comprising:
- a. an epitope-encoding nucleic acid sequence,
- b. optionally a 5′ linker sequence, and
- c. optionally a 3′ linker sequence;
- and
- (ii) optionally, at least one second poly(A) sequence, wherein the second poly(A) sequence is a native poly(A) sequence or an exogenous poly(A) sequence to the alphavirus,
- wherein a first of the at least two cassettes, oriented from 5′ to 3′, is operably linked to a promoter nucleotide sequence comprising a first subgenomic alphavirus-derived promoter (SGP1) comprising a core conserved promoter sequence comprising the polynucleotide sequence ctacggcTAAcctgaa(+1)tgga (SEQ ID NO:
- 27974), and wherein at least a second of the at least two cassettes is operably linked to a promoter nucleotide sequence comprising a second subgenomic alphavirus-derived promoter (SGP2) comprising the core conserved promoter sequence, and
- wherein the SGP1 and/or the SGP2 subgenomic promoter comprises an extended 3′ promoter region derived from an alphavirus encoded 3′ of the core conserved promoter sequence.
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A method for treating a subject, the method comprising administering to the subject a composition for delivery of an antigen expression system comprising a self-replicating alphavirus-based expression system, wherein the composition for delivery of the self-replicating alphavirus-based expression system comprises:
- the self-replicating alphavirus-based expression system, wherein the self-replicating alphavirus-based expression system comprises one or more vectors, wherein the one or more vectors comprise:
- (a) an RNA alphavirus backbone, wherein the RNA alphavirus backbone comprises:
- (i) at least one promoter nucleotide sequence, and
- (ii) at least one polyadenylation (poly(A)) sequence;
- and
- (b) at least two cassettes, wherein each of the cassettes independently comprise:
- (i) at least one antigen-encoding nucleic acid sequence comprising:
- a. an epitope-encoding nucleic acid sequence,
- b. optionally a 5′ linker sequence, and
- c. optionally a 3′ linker sequence;
- and
- (ii) optionally, at least one second poly(A) sequence, wherein the second poly(A) sequence is a native poly(A) sequence or an exogenous poly(A) sequence to the alphavirus,
- wherein a first of the at least two cassettes, oriented from 5′ to 3′, is operably linked to a promoter nucleotide sequence comprising a first subgenomic alphavirus-derived promoter (SGP1) comprising a core conserved promoter sequence comprising the polynucleotide sequence ctacggcTAAcctgaa(+1)tgga, and wherein at least a second of the at least two cassettes is operably linked to a promoter nucleotide sequence comprising a second subgenomic alphavirus-derived promoter (SGP2) comprising the core conserved promoter sequence, and
- wherein the SGP1 and/or the SGP2 subgenomic promoter comprises an extended 3′ promoter region derived from an alphavirus encoded 3′ of the core conserved promoter sequence.
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A composition for delivery of a payload comprising a self-replicating alphavirus-based expression system, wherein the composition for delivery of the self-replicating alphavirus-based expression system comprises:
- the self-replicating alphavirus-based expression system, wherein the self-replicating alphavirus-based expression system comprises one or more vectors, wherein the one or more vectors comprise:
- (a) an RNA alphavirus backbone, wherein the RNA alphavirus backbone comprises:
- (i) at least one promoter nucleotide sequence, and
- (ii) at least one polyadenylation (poly(A)) sequence;
- and
- (b) at least two cassettes, wherein each of the cassettes independently comprise:
- (i) at least one payload-encoding nucleic acid sequence;
- and
- (ii) optionally, at least one second poly(A) sequence, wherein the second poly(A) sequence is a native poly(A) sequence or an exogenous poly(A) sequence to the alphavirus,
- wherein a first of the at least two cassettes, oriented from 5′ to 3′, is operably linked to a promoter nucleotide sequence comprising a first subgenomic alphavirus-derived promoter (SGP1) comprising a core conserved promoter sequence comprising the polynucleotide sequence ctacggcTAAcctgaa(+1)tgga (SEQ ID NO:
- 27974), and wherein at least a second of the at least two cassettes is operably linked to a promoter nucleotide sequence comprising a second subgenomic alphavirus-derived promoter (SGP2) comprising the core conserved promoter sequence, and
- wherein the SGP1 and/or the SGP2 subgenomic promoter comprises an extended 3′ promoter region derived from an alphavirus encoded 3′ of the core conserved promoter sequence.
Dependencies are inferred from the claim text.