Recombinant adenoviruses and use thereof

Patent metadata

Field	Value
Publication number	US-RE50753-E
Application number	US-202217934479-A
Country	US
Kind code	E1
Filing date	Sep 22, 2022
Priority date	Nov 16, 2012
Publication date	Jan 20, 2026
Grant date	Jan 20, 2026

Abstract

The present invention relates to recombinant adenoviruses and vectors thereof. In particular, the adenoviruses are novel simian adenoviruses having a low seroprevalence and high immunogenicity relative to other adenoviruses and vectors thereof. The invention also provides methods for production of the adenoviruses and for the treatment of diseases by administering the adenoviral vector(s) to a subject (e.g., a human).

First claim

What is claimed is:

1 . A recombinant adenovirus comprising a nucleotide sequence having at least 90% sequence identity over the entire sequence of any one of SEQ ID NOs: 10 and 12, or a complementary sequence to a nucleotide sequence having at least 90% sequence identity over the entire sequence of any one of SEQ ID NOs: 10 and 12;
wherein said recombinant adenovirus comprises a deletion in or of an E1 region, an E3 region, and/or an E4 region, said deletion rendering said recombinant adenovirus a replication-defective virus.

2 . The recombinant adenovirus of claim 1 , wherein said nucleotide sequence further comprises all or a portion of any one of SEQ ID NOs: 4, 6, 7, 9, 13, 15, 16, and 18, or a complementary sequence to all or a portion of any one of SEQ ID NOs: 4, 6, 7, 9, 13, 15, 16, and 18.

3 . The recombinant adenovirus of claim 1 , further comprising a nucleotide sequence having at least 90% sequence identity to the sequence of any one of SEQ ID NOs: 1 and 3 or a complementary sequence to a nucleotide sequence having at least 90% sequence identity over the entire sequence of any one of SEQ ID NOs: 1 and 3.

4 . The recombinant adenovirus of claim 2 , wherein said nucleotide sequence comprises the nucleotide sequence of any one of SEQ ID NOs: 34-39 and 46-51.

5 . The recombinant adenovirus of claim 1 , further comprising a heterologous nucleotide sequence encoding an antigenic or therapeutic gene product of interest, or fragment thereof, wherein said antigenic gene product, or fragment thereof, comprises a bacterial, viral, parasitic, or fungal protein, or fragment thereof.

6 . The recombinant adenovirus of claim 5 , wherein:
(i) said bacterial protein, or fragment thereof, is from Mycobacterium tuberculosis, Mycobacterium bovis, Mycobacterium africanum, Mycobacterium microti, Mycobacterium leprae, Pseudomonas aeruginosa, Salmonella typhimurium, Escherichia coli, Klebsiella pneumoniae, Streptococcus pneumoniae, Staphylococcus aureus, Francisella tularensis, Brucella, Burkholderia mallei, Yersinia pestis, Corynebacterium diphtheria, Neisseria meningitidis, Bordetella pertussis, Clostridium tetani, or Bacillus anthracis; (ii) said parasitic protein, or fragment thereof, is from Toxoplasma gondii, Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale, Plasmodium malariae, Trypanosoma spp., or Legionella spp; or (iii) said fungal protein, or fragment thereof, is from Aspergillus, Blastomyces dermatitidis, Candida, Coccidioides immitis, Cryptococcus neoformans, Histoplasma capsulatum var. capsulatum, Paracoccidioides brasiliensis, Sporothrix schenckii, Zygomycetes spp., Absidia corymbifera, Rhizomucor pusillus, or Rhizopus arrhizus.

7 . The recombinant adenovirus of claim 5 , wherein said viral protein, or fragment thereof, is from a viral family selected from the group consisting of Retroviridae, Flaviviridae, Arenaviridae, Bunyaviridae, Filoviridae, Togaviridae, Poxviridae, Herpesviridae, Orthomyxoviridae, Coronaviridae, Rhabdoviridae, Paramyxoviridae, Picornaviridae, Hepadnaviridae, Papillomaviridae, Parvoviridae, Astroviridae, Polyomaviridae, Calciviridae, and Reoviridae, or
said viral protein, or fragment thereof, is from human immunodeficiency virus (HIV), human papillomavirus (HPV), hepatitis A virus (Hep A), hepatitis B virus (HBV), hepatitis C virus (HCV), Variola major, Variola minor, monkeypox virus, measles virus, rubella virus, mumps virus, varicella zoster virus (VZV), poliovirus, rabies virus, Japanese encephalitis virus, herpes simplex virus (HSV), cytomegalovirus (CMV), rotavirus, influenza, Ebola virus, yellow fever virus, Zika virus, or Marburg virus.

8 . The recombinant adenovirus of claim 7 , wherein said viral protein, or fragment thereof, from HIV is Gag, Pol, Env, Nef, Tat, Rev, Vif, Vpr, or Vpu.

9 . A method of treating a subject having a disease, said method comprising administering the recombinant adenovirus of claim 5 to said subject.

10 . The method of claim 9 , wherein said recombinant adenovirus comprises an antigenic gene product, or fragment thereof, that promotes an immune response in said subject against an infective agent, wherein said infective agent is a bacterium, a virus, a parasite, or a fungus.

11 . The method of claim 9 , wherein:
(a) said subject is human; (b) said adenovirus is administered intramuscularly; and/or (c) said adenovirus is administered as a pharmaceutical composition comprising a pharmaceutically acceptable carrier.

12 . The method of claim 11 , wherein:
(i) said subject is administered at least one dose of said pharmaceutical composition; (ii) said subject is administered at least two doses of said pharmaceutical composition; or (iii) said pharmaceutical composition is administered to said subject as a prime boost.

13 . A method of producing a recombinant adenovirus comprising transfecting a cell with: (a) an isolated polynucleotide comprising a nucleotide sequence having at least 90% sequence identity over the entire sequence of any one of SEQ ID NOs: 10 and 12, or a complementary sequence to a nucleotide sequence having at least 90% sequence identity over the entire sequence of any one of SEQ ID NOs: 10 and 12 or (b) a recombinant vector comprising said polynucleotide; culturing said cell in a suitable medium to allow replication of said polynucleotide or vector in said cell; and harvesting produced recombinant adenovirus from said medium and/or said cell.

14 . The method of claim 13 , wherein said cell is a bacterial, plant, or mammalian cell, wherein optionally said mammalian cell is a PER.55K cell or a Chinese hamster ovary (CHO) cell.

15 . The recombinant adenovirus of claim 5 , wherein the viral gene product is an envelope glycoprotein or fragment thereof.

16 . A method of inducing an immune response against a flavivirus in a subject comprising administering the recombinant adenovirus of claim 5 to said subject, wherein the antigenic gene product, or fragment thereof, is a viral gene product from the flavivirus.

17 . The method of claim 16 , wherein the viral gene product is an envelope glycoprotein or fragment thereof.

18 . The method of claim 16 , wherein the subject is a human.

19 . The method of claim 16 , wherein the adenovirus is administered intramuscularly.

20 . The method of claim 16 , wherein the adenovirus is administered as a pharmaceutical composition comprising a pharmaceutically acceptable carrier.

21 . The method of claim 20 , wherein the subject is administered at least one or two doses of the pharmaceutical composition, optionally wherein the pharmaceutical composition is administered to the subject as a prime boost.

22 . A method of inducing an immune response against a retrovirus in a subject comprising administering the recombinant adenovirus of claim 5 to the subject, wherein the antigenic gene product, or fragment thereof, is a viral gene product from the retrovirus.

23 . The method of claim 22 , wherein the retrovirus is human immunodeficiency virus (HIV).

24 . The method of claim 22 , wherein the subject is a human.

25 . The method of claim 22 , wherein the viral gene product is an envelope glycoprotein or fragment thereof.

26 . The method of claim 25 , wherein the viral gene product is a protein or fragment thereof from HIV.

27 . The method of claim 22 , wherein the recombinant adenovirus is administered intramuscularly

Assignees

• Beth Israel Deaconess Medical Ct Inc
• Washington University St Louis

Inventors

• Barouch Dan H
• Virgin Iv Herbert
• Abbink Peter

Classifications

• C12N2710/10042

  virus or viral particle as vehicle, e.g. encapsulating small organic molecule · CPC title

• A61K39/00

  Medicinal preparations containing antigens or antibodies (materials for immunoassay G01N33/53) · CPC title

• C12N2710/10321

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

• C12N2740/15034

  Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein · CPC title

• C12N2710/10343

  viral genome or elements thereof as genetic vector · CPC title