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US 12,616,746 B2Granted
Infectious disease antigens and vaccines
AssigneeSeattle Project Corp.
InventorsAndrew Ferguson, Raphael Rousseau, Roman Yelensky, James Xin Sun, Matthew Joseph Davis, Karin Jooss, Amy Rachel Rappaport, Ciaran Daniel Scallan, Leonid Gitlin, Christine Denise Palmer
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Abstract
Disclosed herein are compositions that include antigen-encoding nucleic acid sequences and/or antigen peptides. Also disclosed are nucleotides, cells, and methods associated with the compositions including their use as vaccines, including vectors and methods for a heterologous prime/boost vaccination strategy.
Claims18
A composition for delivery of a self-replicating alphavirus-based expression system,
- wherein the composition for delivery of the self-replicating alphavirus-based expression system comprises:
- (A) 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 comprises:
- (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) a cassette, wherein the cassette comprises:
- (i) at least one antigen-encoding nucleic acid sequence comprising:
- a. a nucleic acid sequence encoding an infectious disease organism peptide selected from the group consisting of:
- a pathogen-derived peptide, a virus-derived peptide, a bacteria-derived peptide, a fungus-derived peptide, and a parasite-derived peptide,
- b. optionally a 5′ linker sequence, and
- c. optionally a 3′ linker sequence;
- (ii) optionally, a second promoter nucleotide sequence operably linked to the at least one antigen-encoding nucleic acid sequence;
- and
- (iii) 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 an ordered sequence of each element of the cassette in the composition for delivery of the self-replicating alphavirus-based expression system is described in the formula, from 5′ to 3′, comprising:
- Pa-(L5b-Nc-L3d)X-(G5e-Uf)Y-G3g
- wherein P comprises the second promoter nucleotide sequence, where a=0 or 1,
- N comprises one of the epitope-encoding nucleic acid sequences, wherein the epitope-encoding nucleic acid sequence comprises an MHC class I epitope-encoding nucleic acid sequence, where c=1,
- L5 comprises the 5′ linker sequence, where b=0 or 1,
- L3 comprises the 3′ linker sequence, where d=0 or 1,
- G5 comprises one of the at least one nucleic acid sequences encoding a GPGPG amino acid linker, where e=0 or 1,
- G3 comprises one of the at least one nucleic acid sequences encoding a GPGPG amino acid linker, where g=0 or 1,
- U comprises one of the at least one MHC class II epitope-encoding nucleic acid sequence, where f=1,
- X=1 to 400, where for each X the corresponding Nc is an MHC class I epitope-encoding nucleic acid sequence, and
- Y=0, 1, or 2, where for each Y the corresponding Uf is an MHC class II epitope-encoding nucleic acid sequence
- optionally wherein:
- (a) for each X the corresponding Nc is a distinct MHC class I epitope encoding nucleic acid sequence;
- and/or
- (b) for each Y the corresponding Uf is a distinct MHC class II antigen-encoding nucleic acid sequence;
- and/or
- (c) wherein:
- a=0, b=1, d=1, e=1, g=1, h=1, X=20, Y=2,
- the at least one promoter nucleotide sequence is a single 26S promoter nucleotide sequence provided by the backbone,
- the at least one polyadenylation poly(A) sequence is a poly(A) sequence of at least 100 consecutive A nucleotides provided by the backbone,
- each N encodes a MHC class I epitope 7-15 amino acids in length,
- L5 is a native 5′ linker sequence that encodes a native N-terminal amino acid sequence of the MHC I epitope, and wherein the 5′ linker sequence encodes a peptide that is at least 2 amino acids in length,
- L3 is a native 3′ linker sequence that encodes a native C-terminal acid sequence of the MHC I epitope, and wherein the 3′ linker sequence encodes a peptide that is at least 2 amino acids in length,
- U is each of a PADRE class II sequence and a Tetanus toxoid MHC class II sequence,
- wherein the alphavirus vector is a Venezuelan equine encephalitis virus vector,
- each of the MHC class I antigen-encoding nucleic acid sequences encodes a polypeptide that is between 13 and 25 amino acids in length, and
- optionally wherein at least two of the antigen-encoding nucleic acid sequences encode polypeptide sequences or portions thereof that are presented by MHC class I on the tumor cell surface, and
- (B) a lipid-nanoparticle (LNP), wherein the LNP encapsulates the self-replicating alphavirus-based expression system.
40 more elements
A composition for delivery of a self-replicating alphavirus-based expression system,
- wherein the composition for delivery of the self-replicating alphavirus-based expression system comprises:
- (A) 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 comprises:
- (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) a cassette, wherein the cassette comprises:
- (i) at least one antigen-encoding nucleic acid sequence comprising:
- a. a nucleic acid sequence encoding an infectious disease organism peptide selected from the group consisting of:
- a pathogen-derived peptide, a virus-derived peptide, a bacteria-derived peptide, a fungus-derived peptide, and a parasite-derived peptide,
- b. optionally a 5′ linker sequence, and
- c. optionally a 3′ linker sequence;
- (ii) optionally, a second promoter nucleotide sequence operably linked to the at least one antigen-encoding nucleic acid sequence;
- and
- (iii) 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 the at least one promoter nucleotide sequence is:
- the native 26S promoter nucleotide sequence encoded by the RNA alphavirus backbone or wherein the at least one promoter nucleotide sequence is an exogenous RNA promoter;
- and/or
- wherein the second promoter nucleotide sequence is a 26S promoter nucleotide sequence, or comprises multiple 26S promoter nucleotide sequences, wherein each 26S promoter nucleotide sequence provides for transcription of one or more of the separate open reading frames;
- and/or
- the at least one promoter nucleotide sequence or the second promoter nucleotide sequence is inducible or non-inducible;
- and/or
- the at least one poly(A) sequence comprises a poly(A) sequence native to the backbone or exogenous to the backbone;
- and/or
- the at least one poly(A) sequence is operably linked to at least one of the at least one antigen-encoding nucleic acid sequences;
- and/or
- the at least one poly(A) sequence is at least 20, at least 30, at least 40, at least 50, at least 60, at least 70, at least 80, or at least 90 consecutive A nucleotides or at least 100 consecutive A nucleotides, and
- (B) a lipid-nanoparticle (LNP), wherein the LNP encapsulates the self-replicating alphavirus-based expression system.
25 more elements
A composition for delivery of a self-replicating alphavirus-based expression system,
- wherein the composition for delivery of the self-replicating alphavirus-based expression system comprises:
- (A) 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 comprises:
- (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) a cassette, wherein the cassette comprises:
- (i) at least one antigen-encoding nucleic acid sequence comprising:
- a. a nucleic acid sequence encoding an infectious disease organism peptide selected from the group consisting of:
- a pathogen-derived peptide, a virus-derived peptide, a bacteria-derived peptide, a fungus-derived peptide, and a parasite-derived peptide,
- b. optionally a 5′ linker sequence, and
- c. optionally a 3′ linker sequence;
- (ii) optionally, a second promoter nucleotide sequence operably linked to the at least one antigen-encoding nucleic acid sequence;
- and
- (iii) 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 the cassette comprises junctional epitope sequences formed by adjacent sequences in the cassette, optionally wherein:
- at least one or each junctional epitope sequence has an affinity of greater than 500 nM for MHC and/or wherein each junctional epitope sequence is non-self;
- and/or
- the cassette does not encode a non-therapeutic MHC class I or class II epitope nucleic acid sequence comprising a translated, wild-type nucleic acid sequence, wherein the non-therapeutic epitope is predicted to be displayed on an MHC allele of the subject, optionally wherein the non-therapeutic predicted MHC class I or class II epitope sequence is a junctional epitope sequence formed by adjacent sequences in the cassette;
- and/or
- the prediction is based on presentation likelihoods generated by inputting sequences of the non-therapeutic epitopes into a presentation model;
- and/or
- an order of the antigen-encoding nucleic acid sequences in the cassette is determined by a series of steps comprising:
- (a) generating a set of candidate cassette sequences corresponding to different orders of the antigen-encoding nucleic acid sequences;
- (b) determining, for each candidate cassette sequence, a presentation score based on presentation of non-therapeutic epitopes in the candidate cassette sequence;
- and
- (c) selecting a candidate cassette sequence associated with a presentation score below a predetermined threshold as the cassette sequence for a vaccine, and
- (B) a lipid-nanoparticle (LNP), wherein the LNP encapsulates the self-replicating alphavirus-based expression system.
25 more elements
Dependencies are inferred from the claim text.