Adenovirus polynucleotides and polypeptides

Patent metadata

Field	Value
Publication number	US-11795478-B2
Application number	US-202217742221-A
Country	US
Kind code	B2
Filing date	May 11, 2022
Priority date	Dec 9, 2016
Publication date	Oct 24, 2023
Grant date	Oct 24, 2023

Abstract

The present invention relates to isolated polynucleotide and polypeptide sequences derived from novel chimpanzee adenovirus ChAd157, as well as to recombinant polynucleotides, vectors, adenoviruses, cells and compositions comprising said polynucleotide and polypeptide sequences.

First claim

The invention claimed is:

1. An isolated recombinant polynucleotide simian adenoviral vector, wherein the polynucleotide encodes a polypeptide selected from the group consisting of:
(a) a polypeptide having the amino acid sequence according to SEQ ID NO: 1, and
(b) a functional derivative of a polypeptide having the amino acid sequence according to SEQ ID NO: 1, wherein the functional derivative has an amino acid sequence which is at least 99.8% identical over its entire length to the amino acid sequence of SEQ ID NO: 1,

wherein the polynucleotide further encodes a heterologous polypeptide and polynucleotide encoding the heterologous polypeptide is operatively linked to one or more sequences which direct expression of the heterologous polypeptide.

2. A composition comprising the isolated recombinant polynucleotide simian adenoviral vector according to claim 1 , and a pharmaceutically acceptable excipient.

3. A cell comprising the isolated recombinant polynucleotide simian adenoviral vector of claim 1 .

4. The isolated recombinant polynucleotide simian adenoviral vector according to claim 1 , wherein the polynucleotide has a sequence according to SEQ ID NO: 2.

5. The isolated recombinant polynucleotide simian adenoviral vector according to claim 1 , further comprising a polynucleotide encoding:
(a) a polypeptide having the amino acid sequence according to SEQ ID NO: 3; or
(b) a functional derivative of a polypeptide having the amino acid sequence according to SEQ ID NO: 3, wherein the functional derivative has an amino acid sequence which is at least 60% identical over its entire length to the amino acid sequence of SEQ ID NO: 3.

6. The isolated recombinant polynucleotide simian adenoviral vector according to claim 1 , wherein the polynucleotide comprises a sequence according to SEQ ID NO: 4.

7. The isolated recombinant polynucleotide simian adenoviral vector according to claim 1 , further comprising a polynucleotide encoding:
(a) a polypeptide having the amino acid sequence according to SEQ ID NO: 5; or
(b) a functional derivative of a polypeptide having the amino acid sequence according to SEQ ID NO: 5, wherein the functional derivative has an amino acid sequence which is at least 60% identical over its entire length to the amino acid sequence of SEQ ID NO: 5.

8. The isolated recombinant polynucleotide simian adenoviral vector according to claim 1 , wherein the polynucleotide comprises a sequence according to SEQ ID NO: 6.

9. The isolated recombinant polynucleotide simian adenoviral vector according to claim 1 , wherein the polynucleotide comprises at least one of the following:
(a) an adenoviral 5′ inverted terminal repeat;
(b) an adenoviral E1A region, or a fragment thereof selected from an E1A_280R region and an E1A_243R region;
(c) an adenoviral E1B or IX region, or a fragment thereof selected from an E1B_19K region, an E1B_55K region and an IX region;
(d) an adenoviral E2b region; or a fragment thereof selected from an E2B_pTP region, an E2B_Polymerase region and an E2B_IVa2 region;
(e) an adenoviral L1 region, or a fragment thereof, said fragment encoding an adenoviral protein selected from an L1_13.6k protein, an L1_52k protein and an L1_IIIa protein;
(f) an adenoviral L2 region, or a fragment thereof, said fragment encoding an adenoviral protein selected from an L2_penton protein, an L2_pVII, L2_V protein, and an L2_pX protein;
(g) an adenoviral L3 region, or a fragment thereof, said fragment encoding an adenoviral protein selected from an L3_pVI protein, an L3_hexon protein and an L3_protease;
(h) an adenoviral E2A region;
(i) an adenoviral L4 region, or a fragment thereof said fragment encoding an adenoviral protein selected from an L4_100k protein, an L4_33k protein and an protein L4_VIII protein;
(j) an adenoviral E3 region, or a fragment thereof selected from E3 ORF1, E3 ORF2, E3 ORF3, E3 ORF4, E3 ORF5, E3 ORF6, E3 ORF7, E3 ORF8, and E3 ORF9;
(k) an adenoviral L5 region, or a fragment thereof said fragment encoding an L5_fiber protein;
(l) an adenoviral E4 region, or a fragment thereof selected from E4 ORF7, E4 ORF6, E4 ORF4, E4 ORF3, E4 ORF2, and E4 ORF1;
(m) an adenoviral 3′ inverted terminal repeat; and/or
(n) an adenoviral VAI or VAII RNA region from an adenovirus other than ChAd157.

10. The isolated recombinant polynucleotide simian adenoviral vector according to claim 1 , wherein the polynucleotide comprises a polynucleotide which is at least 95% identical over its entire length to a reference sequence that consists essentially of SEQ ID NO: 15 or 22.

11. The isolated recombinant polynucleotide simian adenoviral vector according to claim 10 , wherein the polynucleotide comprises or consists of a polynucleotide which is at least 99.5% identical over its entire length to the reference sequence.

12. The isolated recombinant polynucleotide simian adenoviral vector according to claim 11 , wherein the polynucleotide comprises or consists of a polynucleotide which is identical over its entire length to the reference sequence.

13. The isolated recombinant polynucleotide simian adenoviral vector according to claim 1 , wherein the adenoviral vector is replication competent.

14. The isolated recombinant polynucleotide simian adenoviral vector according to claim 1 , wherein the adenoviral vector is replication incompetent.

15. The isolated recombinant polynucleotide simian adenoviral vector according to claim 14 , wherein the adenoviral vector comprises a functional inactivation.

16. The isolated recombinant polynucleotide simian adenoviral vector according to claim 1 , wherein the functional inactivation is a deletion.

17. The isolated recombinant polynucleotide simian adenoviral vector according to claim 1 , wherein the functional inactivation comprises a mutation or deletion which renders non-functional at least one gene of a genomic region selected from the group consisting of E1A, E1B, E2A, E2B, E3 and E4.

18. The isolated recombinant polynucleotide simian adenoviral vector according to claim 1 , wherein the heterologous polypeptide is an antigenic protein or a fragment thereof.

19. The isolated recombinant polynucleotide simian adenoviral vector of claim 1 , wherein the one or more sequences which direct expression of the heterologous polypeptide is selected from one or more of the group consisting of transcription initiation, transcription termination, promoter and enhancer sequences.

20. The composition according to claim 2 , further comprising an adjuvant.

21. The cell according to claim 3 , wherein the cell is a host cell that expresses at least one adenoviral gene selected from the group consisting of E1A, E1B, E2A, E2B, E3 E4, L1, L2, L3, L4 and L5.

22. A method for eliciting an immune response in a subject comprising
(a) administering to the subject the recombinant adenoviral vector according to claim 1 encoding a first heterologous polypeptide; and
(b) administering to the subject a recombinant adenoviral vector which does not comprise a ChAd157 fiber, the vector encoding a second heterologous polypeptide,

wherein steps (a) and (b) may be undertaken in either order and the first and second heterologous polypeptides may be the same or different.

23. The method according to claim 22 , wherein the subject has previously been exposed to a recombinant adenoviral vector which does not comprise a ChAd157 fiber, or functional derivative thereof.

24. The method according to claim 23

Assignees

• Glaxosmithkline Biologicals Sa

Inventors

• Ammendola Virginia
• Capone Stefania
• Colloca Stefano
• Folgori Antonella
• Merone Rossella

Classifications

• C12N15/86 Primary

  Viral vectors · CPC title

• A61K39/12

  Viral antigens · CPC title

• A61K39/21

  Retroviridae, e.g. equine infectious anemia virus · CPC title

• A61P31/14

  for RNA viruses · CPC title

• A61P31/18

  for HIV · CPC title