PR13.5 promoter for robust T-cell and antibody responses
AssigneeBavarian Nordic A/S
InventorsRobin Steigerwald, Kay Brinkmann
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Abstract
The invention encompasses recombinant poxviruses, preferably modified Vaccinia Ankara (MVA) viruses, comprising a Pr13.5 promoter operably linked to a nucleotide sequence encoding an antigen and uses thereof. The invention is drawn to compositions and methods for the induction of strong CD8 T cell and antibody responses to a specific antigen(s) by administering one or more immunizations of the recombinant MVA to a mammal, preferably a human.
Claims8
A method of inducing an antibody response and/or a CD8 T-cell response against a neoantigen in a human comprising administering one or more administrations of a recombinant modified Vaccinia Ankara (MVA) virus to the human;
- wherein the recombinant MVA comprises a Pr13.5 promoter operably linked to a nucleotide sequence encoding the neoantigen,
- wherein the Pr13.5 promoter comprises at least 1 copy of a first nucleotide sequence set forth in any one of SEQ ID NOs:8-27 and at least 1 copy of a second nucleotide sequence set forth in any one of SEQ ID NOs:8-27, and
- wherein said first nucleotide sequence and said second nucleotide sequence are separated by 20-80 nucleotides.
A method of inducing an immunodominant T cell response against a neoantigen in a human comprising administering one or more administrations of a recombinant modified Vaccinia Ankara (MVA) virus to the human;
- wherein the recombinant MVA comprises a Pr13.5 promoter operably linked to a nucleotide sequence encoding the neoantigen,
- wherein the Pr13.5 promoter comprises at least 1 copy of a first nucleotide sequence set forth in any one of SEQ ID NOs:8-27 and at least 1 copy of a second nucleotide sequence set forth in any one of SEQ ID NOs:8-27, wherein said first nucleotide sequence and said second nucleotide sequence are separated by 20-80 nucleotides;
- and
- wherein the immunodominant T cell response against the neoantigen is greater than a T cell response to a poxviral antigen.
A recombinant modified Vaccinia Ankara (MVA) virus comprising a Pr13.5 promoter operably linked to a nucleotide sequence encoding a neoantigen, wherein the Pr13.5 promoter comprises at least 1 copy of a first nucleotide sequence set forth in any one of SEQ ID NOs:8-27 and at least 1 copy of a second nucleotide sequence set forth in any one of SEQ ID NOs:8-27, and wherein said first nucleotide sequence and said second nucleotide sequence are separated by 20-80 nucleotides.
Dependencies are inferred from the claim text.