Recombinant adenoviruses and uses thereof

Patent metadata

Field	Value
Publication number	US-11773142-B2
Application number	US-201816772045-A
Country	US
Kind code	B2
Filing date	Dec 11, 2018
Priority date	Dec 11, 2017
Publication date	Oct 3, 2023
Grant date	Oct 3, 2023

Abstract

Featured are recombinant adenoviruses and vectors thereof. In particular, the adenoviruses are simian (rhesus) adenoviruses having a low seroprevalence and high immunogenicity (when expressing, e.g., an antigenic polypeptide) relative to other adenoviruses and vectors thereof. Also featured are methods for producing the adenoviruses and methods of treatment of diseases by administering the adenoviral vector(s) to a subject (e.g., a human).

First claim

The invention claimed is:

1. A recombinant adenovirus comprising:
(I) a nucleotide sequence encoding a hexon protein, wherein:
(a) the nucleotide sequence encoding the hexon protein has at least 93% sequence identity over the entire sequence of SEQ ID NO: 56; or
(b) the hexon protein comprises 99% or greater sequence identity over the entire amino acid sequence of SEQ ID NO: 160;

(II) a nucleotide sequence encoding a short fiber protein, a long fiber protein, and/or a penton protein, wherein:
(a) the nucleotide sequence encoding the short fiber protein has at least 85% identity to the nucleotide sequence of SEQ ID NO: 19;
(b) the short fiber protein has at least 85% identity to the amino acid sequence of SEQ ID NO: 123;
(c) the nucleotide sequence encoding the long fiber protein has at least 90% identity to the nucleotide sequence of SEQ ID NO: 42;
(d) the long fiber protein has at least 90% identity to the amino acid sequence of SEQ ID NO: 146;
(e) the nucleotide sequence encoding the penton protein has at least 95% sequence identity over the entire sequence of SEQ ID NO: 108, and/or
(f) the penton protein comprises 96% or greater sequence identity over the entire amino acid sequence of SEQ ID NO: 212; and

(III) a deletion in or of the E1, E2, and/or E3 region.

2. The recombinant adenovirus of claim 1 , wherein:
(I) the nucleotide sequence encoding the hexon protein of (I)(a) has:
(a) at least 94%, 95%, 96%, 97%, 98%, 99%, and 100% sequence identity over the entire sequence of SEQ ID NO: 56; or

(II) the nucleotide sequence encoding the hexon protein of (I)(b) has 100% sequence identity over the entire sequence of SEQ ID NO: 160.

3. The recombinant adenovirus of claim 1 , wherein:
(I) the nucleotide sequence encoding the short fiber protein has at least 90%, 92%, 95%, 97%, 99%, or 100% sequence identity to all or a part of the nucleic acid sequence of SEQ ID NO: 19;

(II) the nucleotide sequence encoding the long fiber protein has at least 91%, 92%, 95%, 97%, 98%, 99%, or 100% sequence identity to all or a part of the nucleic acid sequence of SEQ ID NO: 42; and/or
(III) the nucleotide sequence encoding the penton protein has at least 97%, 99%, or 100% sequence identity to all or a part of the nucleic acid sequence of SEQ ID NO: 108.

4. The recombinant adenovirus of claim 1 , wherein:
(I) the short fiber protein has at least 90%, 92%, 95%, 97%, 98%, 99%, or 100% sequence identity to all or a part of the amino acid sequence of SEQ ID NO: 123;
(II) the long fiber protein has at least 91%, 92%, 95%, 97%, 98%, 99%, or 100% sequence identity to all or a part of the amino acid sequence of SEQ ID NO: 146; and/or
(III) the penton protein has at least 97%, 98%, 99%, or 100% sequence identity to all or a part of the amino acid sequence of SEQ ID NO: 212.

5. The recombinant adenovirus of claim 1 , wherein the recombinant adenovirus is a replication-defective virus, binds a sialic acid receptor, and/or further comprises a heterologous nucleotide sequence encoding an antigenic or therapeutic gene product or fragment thereof.

6. The recombinant adenovirus of claim 5 , wherein the recombinant adenovirus further comprises the antigenic gene product or fragment thereof, wherein the antigenic gene product or fragment thereof comprises a bacterial protein or fragment thereof; a viral protein or fragment thereof; a parasitic protein or fragment thereof; or a fungal protein or fragment thereof.

7. The recombinant adenovirus of claim 6 , wherein:
(I) the 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) the viral protein or fragment thereof, is:
(a) 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;
(b) 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; and/or
(c) an envelope glycoprotein or fragment thereof;

(III) the parasitic protein or fragment thereof, is from Toxoplasma gondii, Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale, Plasmodium malariae, Trypanosoma spp., or Legionella spp.; or
(IV) the 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.

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

9. A method of inducing an immune response or treating a disease in a subject, the method comprising administering the recombinant adenovirus of claim 1 to the subject.

10. The method of claim 9 , wherein the recombinant adenovirus comprises an antigenic gene product or fragment thereof, that promotes an immune response in the subject against an infective agent.

11. The method of claim 10 , wherein:
(I) the immune response comprises a decrease in expression of interleukin-9 (IL9) relative to a reference level;
(II) the antigenic gene product or fragment thereof, comprises a bacterial protein or fragment thereof, a viral protein or fragment thereof, a parasitic protein or fragment thereof, or a fungal protein or fragment thereof; or
(III) the infective agent is a bacterium, a virus, a parasite, or a fungus.

12. The method of claim 11 , wherein:
(I) the 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) the viral protein or fragment thereof is:
(a) 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;
(b) 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

Assignees

• Beth Israel Deaconess Medical Ct Inc

Inventors

• Barouch Dan H
• Abbink Peter
• Iampietro Mark Justin
• Havenga Menzo J E

Classifications

• A61K39/0011

  Cancer antigens · CPC title

• C07K14/075 Primary

  Adenoviridae · CPC title

• A61K31/7088

  Compounds having three or more nucleosides or nucleotides · CPC title

• A61K35/761

  Adenovirus · CPC title

• A61K39/235

  Adenoviridae · CPC title