Adenoviral vectors with two expression cassettes encoding RSV antigenic proteins or fragments thereof

Patent metadata

Field	Value
Publication number	US-11859199-B2
Application number	US-201816756380-A
Country	US
Kind code	B2
Filing date	Oct 16, 2018
Priority date	Oct 16, 2017
Publication date	Jan 2, 2024
Grant date	Jan 2, 2024

Abstract

An adenoviral vector comprising two expression cassettes, wherein each expression cassette comprises a transgene and a promoter, and wherein each transgene encodes an RSV antigenic protein or a fragment thereof.

First claim

The invention claimed is:

1. A simian adenoviral vector comprising two expression cassettes, wherein each expression cassette comprises a transgene and a promoter, wherein the first expression cassette is inserted in the E1 region of the simian adenoviral vector, and the second expression cassette is inserted in a region of the adenoviral vector that is compatible with vector replication; the transgene of the first and second expression cassettes comprise a respiratory syncytial virus antigen; and the first expression cassette and/or the second expression cassette comprises an enhanced human CMV promoter having a nucleic acid sequence having at least about 90% sequence identity to SEQ ID NO:6.

2. The simian adenoviral vector of claim 1 , wherein the respiratory syncytial antigen is selected from one or more of the fusion (F) protein, the attachment (G) protein, the matrix (M2) protein and the nucleoprotein (N).

3. The simian adenoviral vector of claim 2 , wherein at least one respiratory syncytial antigen is a fusion (F) protein.

4. The simian adenoviral vector of claim 1 , wherein the second expression cassette is inserted in the E3 region, between the stop codons of L5 and E4 (the “HE1” region) or between the end of the ITR and the cap site of E4 mRNA (the “HE2” region) of the simian adenoviral vector.

5. The simian adenoviral vector of claim 4 , wherein the second expression cassette is inserted in the E3 region of the simian adenoviral vector.

6. The simian adenoviral vector of claim 4 , wherein the second expression cassette is inserted in the HE1 region of the simian adenoviral vector.

7. The simian adenoviral vector of claim 4 , wherein the second expression cassette is inserted in the HE2 region of the simian adenoviral vector.

8. The simian adenoviral vector of claim 1 , wherein the vector is a chimpanzee adenoviral vector.

9. The simian adenoviral vector of claim 1 , wherein the vector is an adenovirus.

10. The simian adenoviral vector of claim 1 , wherein the enhanced hCMV promoter has a nucleic acid sequence having at least about 96% sequence identity to SEQ ID NO: 6.

11. The simian adenoviral vector of claim 1 , wherein the promoter comprises the nucleic acid sequence of SEQ ID NO: 6.

12. The simian adenoviral vector of claim 1 , wherein the first and second expression cassettes comprise different promoters.

13. The simian adenoviral vector of claim 1 , wherein the adenoviral vector is capable of infecting a mammalian cell.

14. The simian adenoviral vector of claim 1 , wherein the first and/or the second expression cassette further comprises a posttranscriptional regulatory element.

15. The simian adenoviral vector of claim 14 , wherein the posttranscriptional regulatory element is a Woodchuck Hepatitis Postranscriptional Regulatory Element.

16. A composition comprising the simian adenoviral vector of claim 1 and a pharmaceutically acceptable excipient.

17. A method of inducing an immune response against respiratory syncytial virus in a subject in need thereof comprising administering an immunologically effective amount of the simian adenoviral vector of claim 1 to the subject.

18. The method of claim 17 , wherein the simian adenoviral vector is a vaccine component.

Assignees

• Glaxosmithkline Biologicals Sa

Inventors

• Colloca Stefano

Classifications

• C12N15/86 Primary

  Viral vectors · CPC title

• A61K39/235

  Adenoviridae · CPC title

• C12N2710/10343

  viral genome or elements thereof as genetic vector · CPC title

• C12N2710/16121

  Viruses as such, e.g. new isolates, mutants or their genomic sequences · CPC title

• C12N2830/48

  regulating transport or export of RNA, e.g. RRE, PRE, WPRE, CTE · CPC title