Universal t cell-based, cmv-vectored vaccine for influenza
AssigneeOregon Health & Science University
InventorsJonah SACHA, Louis PICKER, Daniel MALOULI, Scott HANSEN, Klaus FRUEH
Life of this patent
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Abstract
The invention relates to methods of generating an immune response for the treatment or prevention of a pathogenic infection. The invention also relates to methods of generating MHC-I, MHC-II, and/or MHC-E restricted CD8+ and/or CD4+ T cells for the treatment or prevention of a pathogenic infection.
Claims174
A recombinant cytomegalovirus (CMV) vector comprising:
- (a) a first nucleic acid sequence encoding an influenza matrix protein;
- (b) a second nucleic acid sequence encoding an influenza nucleoprotein;
- and
- (c) a third nucleic acid sequence encoding an influenza polymerase.
A recombinant cytomegalovirus (CMV) vector comprising:
- (a) a first nucleic acid sequence encoding an influenza matrix;
- and/or
- (b) a second nucleic acid sequence encoding an influenza nucleoprotein;
- and/or
- (c) a third nucleic acid sequence encoding an influenza polymerase;
- wherein the vector does not express an active UL128 protein or ortholog thereof;
- does not express an active UL130 protein or ortholog thereof;
- does not express an active UL 146 protein or ortholog thereof;
- does not express an active UL 147 protein or ortholog thereof;
- and does not express an active UL18 protein or ortholog thereof.
The CMV vector of any of the preceding claims, wherein the CMV vector does not express an active pp71 protein or ortholog thereof.
The CMV vector of any one of the preceding claims, wherein the CMV vector is a human CMV (HCMV) vector, a rhesus macaque CMV (RhCMV) vector, or a cynomolgus macaque CMV (CyCMV) vector.
The CMV vector of any of the preceding claims, wherein at least one of the influenza matrix protein, influenza nucleoprotein, or influenza polymerase is derived from a H1N1 influenza virus.
The CMV vector of any of the preceding claims, wherein the influenza matrix protein, influenza nucleoprotein, and influenza polymerase are derived from a H1N1 influenza virus.
The CMV vector of any of the preceding claims, wherein at least one of the influenza matrix protein, influenza nucleoprotein, or influenza polymerase is derived from a 1918 H1N1 influenza virus.
The CMV vector of any of the preceding claims, wherein the influenza matrix protein, influenza nucleoprotein, and influenza polymerase are derived from a 1918 H1N1 influenza virus.
The CMV vector of any of the preceding claims, wherein the nucleic acid sequence encoding the matrix protein is a wild-type or a codon-optimized nucleic acid sequence.
The CMV vector of any of the preceding claims, wherein the nucleic acid sequence encoding the matrix protein has at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to the sequence of SEQ ID NO:
- 1.
The CMV vector of any of the preceding claims, wherein the matrix protein has an amino acid sequence with at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to the sequence of SEQ ID NO:
- 10.
The CMV vector of any of the preceding claims, wherein the nucleic acid sequence encoding the nucleoprotein is a wild-type or a codon-optimized nucleic acid sequence.
The CMV vector of any of the preceding claims, wherein the nucleic acid sequence encoding the nucleoprotein has at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to the sequence of SEQ ID NO:
- 3.
The CMV vector of any of the preceding claims, wherein the nucleoprotein has an amino acid sequence with at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to the sequence of SEQ ID NO:
- 12.
The CMV vector of any of the preceding claims, wherein the nucleic acid sequence encoding the polymerase encodes a polymerase basic 1 (PB1) protein, a polymerase basic 2 (PB2) protein, or a polymerase acidic protein.
The CMV vector of any one of the preceding claims, wherein the nucleic acid sequence encoding the polymerase is a wild-type or a codon-optimized nucleic acid sequence.
The CMV vector of any of the preceding claims, wherein the nucleic acid sequence encoding the polymerase has at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to the sequence of SEQ ID NO:
- 5.
The CMV vector of any of the preceding claims, wherein the polymerase has an amino acid sequence with at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to the sequence of SEQ ID NO:
- 14.
The CMV vector of any one of the preceding claims, wherein the nucleic acid sequence encoding the matrix protein, the nucleic acid sequence encoding the nucleoprotein, and the nucleic acid sequence encoding the polymerase are under the transcriptional control of a UL82 promoter, CMV promoter, a CMV-gH promoter, a HCMV promoter, a RhCMV promoter, a EF1α promoter, a CAG promoter, or a MCMV promoter.
A recombinant cynomolgus cytomegalovirus (CyCMV) vector comprising at least one heterologous antigen, wherein the vector does not express an active UL128 protein or ortholog thereof;
- does not express an active UL130 protein or ortholog thereof;
- and does not express an active UL146 protein or ortholog thereof.
Dependencies are inferred from the claim text.