PR13.5 promoter for robust T-cell and antibody responses

Patent metadata

Field	Value
Publication number	US-11028130-B2
Application number	US-201715821035-A
Country	US
Kind code	B2
Filing date	Nov 22, 2017
Priority date	Oct 28, 2012
Publication date	Jun 8, 2021
Grant date	Jun 8, 2021

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.

First claim

We claim:

1. 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.

2. 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.

3. The method of claim 2 , wherein the immunodominant T cell response is at least 2, 3, 4, or 5 fold greater than the T-cell response to the poxviral antigen.

4. The method of claim 2 , wherein the poxviral antigen is B8R.

5. 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.

6. The method of claim 1 , wherein said first nucleotide sequence and said second nucleotide sequence are separated by 30-40 nucleotides.

7. The method of claim 2 , wherein said first nucleotide sequence and said second nucleotide sequence are separated by 30-40 nucleotides.

8. The recombinant MVA of claim 5 , wherein said first nucleotide sequence and said second nucleotide sequence are separated by 30-40 nucleotides.

Assignees

• Bavarian Nordic As

Inventors

• Steigerwald Robin
• Brinkmann Kay

Classifications

• C12N2830/60

  from viruses · CPC title

• C12N7/00

  Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof (preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00) · CPC title

• A61K2039/572

  cytotoxic response · CPC title

• C12N2710/24122

  New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes · CPC title

• C12N15/86 Primary

  Viral vectors · CPC title