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US 11,510,973 B2Granted
Alphavirus antigen vectors
AssigneeGritstone Bio, Inc.
InventorsWade Blair, Karin Jooss, Amy Rachel Rappaport, Ciaran Daniel Scallan, Leonid Gitlin
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Abstract
Disclosed herein are alphavirus vectors that include neoantigen-encoding nucleic acid sequences derived from a tumor of a subject. Also disclosed are nucleotides, cells, and methods associated with the vectors including their use as vaccines.
Claims57
A composition for delivery of an antigen expression system, comprising:
- the antigen expression system,
- wherein the antigen expression system comprises one or more vectors,
- the one or more vectors comprising:
- (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) an antigen cassette, wherein the antigen cassette comprises:
- (I) at least two antigen-encoding nucleic acid sequences, each comprising:
- (A) an epitope encoding nucleic acid sequence, and
- (B) a native 5′ linker sequence that encodes a native N-terminal amino acid sequence of the epitope, and wherein the 5′ linker sequence encodes a peptide that is between 2-20 amino acids in length, and
- (C) a native 3′ linker sequence that encodes a native C-terminal amino acid sequence of the epitope, and wherein the 3′ linker sequence encodes a peptide that is between 2-20 amino acids in length,
- wherein each of the at least two antigen-encoding nucleic acid sequences is linked directly to one another.
10 more elements
A method for inducing an immune response in a subject, the method comprising administering to the subject an antigen expression system, comprising:
- the antigen expression system,
- wherein the antigen expression system comprises one or more vectors,
- the one or more vectors comprising:
- (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) an antigen cassette, wherein the antigen cassette comprises:
- (I) at least two antigen-encoding nucleic acid sequences, each comprising:
- (A) an epitope encoding nucleic acid sequence, and
- (B) a native 5′ linker sequence that encodes a native N-terminal amino acid sequence of the epitope, and wherein the 5′ linker sequence encodes a peptide that is between 2-20 amino acids in length, and
- (C) a native 3′ linker sequence that encodes a native C-terminal amino acid sequence of the epitope, and wherein the 3′ linker sequence encodes a peptide that is between 2-20 amino acids in length,
- wherein each of the at least two antigen-encoding nucleic acid sequences is linked directly to one another.
10 more elements
A composition for delivery of an antigen expression system, comprising:
- the antigen expression system,
- wherein the antigen expression system comprises one or more vectors,
- the one or more vectors comprising:
- (a) an RNA alphavirus backbone, wherein the RNA alphavirus backbone comprises the sequence set forth in SEQ ID NO:6;
- and
- (b) an antigen cassette, wherein the antigen cassette comprises:
- (I) at least one antigen-encoding nucleic acid sequence, comprising:
- (A) an epitope encoding nucleic acid sequence, and
- (B) optionally, a 5′ linker sequence, and
- (C) optionally, a 3′ linker sequence.
7 more elements
A composition for delivery of an antigen expression system, comprising:
- the antigen expression system,
- wherein the antigen expression system comprises one or more vectors,
- the one or more vectors comprising:
- (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) an antigen cassette, wherein the antigen cassette comprises:
- (I) at least two antigen-encoding nucleic acid sequence, each comprising:
- (A) an epitope encoding nucleic acid sequence, and
- (B) optionally, a 5′ linker sequence, and
- (C) optionally, a 3′ linker sequence;
- wherein the antigen cassette comprises junctional epitope sequences encoded by adjacent antigen-encoding nucleic acid sequences in the antigen cassette, wherein at least one or each junctional epitope sequence has an affinity of greater than 500 nM for MEW, and optionally wherein at least one or each junctional epitope sequence is non-self.
10 more elements
Dependencies are inferred from the claim text.