Modified immunization vectors

• US 9,670,506 B2
• Filed: 04/29/2010
• Issued: 06/06/2017
• Est. Priority Date: 04/30/2009
• Status: Active Grant

• Current Assignee: Consejo Superior de Investigaciones Científicas,, Ippox Foundation, Arizona Board of Regents (University of Arizona)
• Original Assignee: Academisch Zikenhuis Leiden, Centre Hospitalier Universitaire Vaudois, Consejo Superior de Investigaciones Científicas,, Sanofi Pasteur Limited (Sanofi ), Universite De Montreal, L', Arizona Board of Regents (University of Arizona)
• Inventors: Pantaleo, Giuseppe, Harari, Alexandre, Calandra, Thierry, Roger, Thierry, Esteban, Mariano, Kibler, Karen, Melief, Cornelius, Jacobs, Bertram, Sekaly, Rafick-Pierre, Haddad, Elias, Tartaglia, James
• Primary Examiner(s): Blumel, Benjamin P
• Application Number:
  US13/266,282
• Publication Number:
  US 20120328653A1
• Time in Patent Office: 2,595 Days
• Field of Search: None
• CPC Class Codes: A61K 2039/5256 expressing foreign proteins
• CPC Class Codes: A61K 39/12 Viral antigens
• CPC Class Codes: A61K 39/275 Poxviridae, e.g. avipoxvirus
• CPC Class Codes: A61K 39/295 Polyvalent viral antigens vaccinia virus or variola virus A61K39/285; Mixtures of viral and bacterial antigens
• CPC Class Codes: A61K 49/00 Preparations for testing in vivo
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: C12N 15/86 Viral vectors
• CPC Class Codes: C12N 2710/24143 viral genome or elements thereof as genetic vector
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The disclosure relates to recombinant vectors and methods for using the same. In certain embodiments, the recombinant vectors are immunogenic.

Claims

1. A recombinant NYVAC vector encoding in its genome C7L (SEQ ID NO:

17) and K1L (SEQ ID NO;

     27), wherein the C7L (SEQ ID NO;

     17) and K1L (SEQ ID NO;

     27) coding sequences are adjacent to one another in the genome.

2. The recombinant NYVAC vector of claim 1, further comprising a polynucleotide encoding Ambystoma tigrinum virus Eukaryotic Translation Initiation Factor (ATV elF2α

H) (SEQ ID NO.

     29).

3. The recombinant NYVAC vector of claim 1, the vector further comprising a polynucleotide encoding an immunogen.

4. The recombinant NYVAC vector of claim 3, wherein the immunogen directs an immune response against an antigen selected from the group consisting of a viral target antigen, a bacterial target antigen, a parasitic target antigen, or a tumor target antigen.

5. The recombinant NYVAC vector of claim 4, wherein the viral target antigen is derived from a virus selected from the group consisting of an adenovirus, herpes virus, epstein-barr virus, human cytomegalovirus, varicella-zoster virus, poxvirus, parvovirus, papillomavirus, reovirus, picornavirus, coxsackie virus, hepatitis A virus, poliovirus, togavirus, rubella virus, flavivirus, hepatitis C virus, yellow fever virus, dengue virus, west Nile virus, orthomyxovirus, influenza virus, rhabdovirus, paramyxovirus, measles virus, mumps virus, parainfluenza virus, respiratory syncytial virus, rhabdovirus, rabies virus, retrovirus, human immunodeficiency virus (HIV), hepadnavirus, and hepatitis B virus.

6. The recombinant NYVAC vector of claim 5, wherein the virus is human immunodeficiency virus (HIV).

7. The recombinant NYVAC vector of claim 6, wherein the immunogen is encoded by the genome of HIV-1 intersubtype (C/B′

).

8. The recombinant NYVAC vector of claim 6, wherein the immunogen is selected from the group consisting of Env, Gag, Nef, and Pol.

9. The recombinant NYVAC vector of claim 8, wherein the immunogen is provided by a GAG-POL-NEF fusion protein.

10. The recombinant NYVAC vector of claim 6, wherein the immunogen has the amino acid sequence selected from the group consisting of ENV, GAG, POL, NEF, VGNLWVTVYYGVPVW (SEQ ID NO. 56), WVTVYYGVPVWKGAT (SEQ ID NO. 57), GATTTLFCASDAKAY (SEQ ID NO. 58), TTLFCASDAKAYDTE (SEQ ID NO. 59), THACVPADPNPQEMV (SEQ ID NO. 60), ENVTENFNMWKNEMV (SEQ ID NO. 61), ENFNMWKNEMVNQMQ (SEQ ID NO. 62), EMVNQMQEDVISLWD (SEQ ID NO. 63), CVKLTPLCVTLECRN (SEQ ID NO. 64), NCSFNATTVVRDRKQ (SEQ ID NO. 65), NATTVVRDRKQTVYA (SEQ ID NO. 66), VYALFYRLDIVPLTK (SEQ ID NO. 67), FYRLDIVPLTKKNYS (SEQ ID NO. 68), INCNTSAITQACPKV (SEQ ID NO. 69), PKVTFDPIPIHYCTP (SEQ ID NO. 70), FDPIPIHYCTPAGYA (SEQ ID NO. 71), TGDIIGDIRQAHCNI (SEQ ID NO. 72), SSSIITIPCRIKQII (SEQ ID NO. 73), ITIPCRIKQIINMWQ (SEQ ID NO. 74), CRIKQIINMWQEVGR (SEQ ID NO. 75), VGRAMYAPPIKGNIT (SEQ ID NO. 76), MYAPPIKGNITCKSN (SEQ ID NO. 77), PIKGNITCKSNITGL (SEQ ID NO. 78), ETFRPGGGDMRNNWR (SEQ ID NO. 79), ELYKYKVVEIKPLGV (SEQ ID NO. 80), YKVVEIKPLGVAPTT (SEQ ID NO. 81), EIKPLGVAPTTTKRR (SEQ ID NO. 82), LGVAPTTTKRRVVER (SEQ ID NO. 83), and YSENSSEYY (SEQ ID NO. 84).

11. The recombinant NYVAC vector of claim 4, wherein the bacterial target antigen is derived from a bacterial organism selected from the group consisting of Bacillus anthracis, Bordetella pertussis, Borrelia burgdorferi, Bmeella abortus, Brucella canis, Brucella melitensis, Brucella suis, Campylobacter jejuni, Chlamydia pneumoniae, Chlamydia psittaci, Chlamydia trachomatis, Clostridium botulinum, Clostridium difficile, Clostridium perfringens, Clostridium tetani, Corynebacterium diptheriae, Enterococcus faecalis, enterococcus faecum, Escherichia coli, Francisella tularensis, Haemophilus influenza, Helicobacter pylori, Legionella pneumophila, Leptospira interrogans, Listeria monocytogenes, Mycobacterium leprae, Mycobacterium tuberculosis, Mycoplasma pneumoniae, Neisseria gonorrhea, Neisseria meningitidis, Pseudomonas aeruginosa, Rickettsia rickettsii, Salmonella typhi, Salmonella typhinurium, Shigella sonnei, Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus saprophyticus, coagulase negative staphylococcus, Streptococcus agalactiae, Streptococcus pneumoniae, Streptococcus pyrogenes, Treponema pallidum, Vibrio cholerae, and Yersinia pestis.

12. The recombinant NYVAC vector of claim 4, wherein the parasite target antigen is derived from a bacterial organism selected from the group consisting of

Ancylostoma duodenale, Anisakis spp., Ascaris lumbricoides, Balantidium coli, Cestoda spp., Cimicidae spp., Clonorchis sinensis, Dicrocoelium dendriticum, Dicrocoelium hospes, Diphyllobothrium latum, Dracunculus spp., Echinococcus granulosus, Echinococcus multif ocularis, Entamoeba histolytica, Enterobius vermicularis, Fasciola hepatica, Fasciola magna, Fasciola gigantica, Fasciola jacksoni, Fasciolopsis buski, Giardia lamblia, Gnathostoma spp., Hymenolepis nana, Hymenolepis diminuta, Leishmania spp., Loa boa, Metorchis conjunctus, Metorchis albidus, Necator americanus, Oestroidea spp., Onchocercidae spp., Opisthorchis viverrini, Opisthorchis felineus, Opisthorchis guayaquilensis, Opisthorchis noverca, Plasmodium falciparum, Protofasciola robusta, Parafasciolopsis fasc-iomorphae, Paragonimus westermani, Schistosoma mansoni, Schistosoma japonicum, Schistosoma mekongi, Schistosoma haematobium, Spirometra erinaceieuropaei, Strongyloides stercoralis, Taenia saginata, Taenia solium, Toxocara canis, Toxocara cati, Toxoplasma gondii, Trichobilharzia regent, Trichinella spiralis, Trichuris trichiura, Trombiculidae spp., Trypanosoma spp., Tungapenetrans, and Wuchereria bancrofti.

13. The recombinant NYVAC vector of claim 4, wherein the tumor target antigen is selected from the group consisting of:

a gp100 (MART-1/Melan A), gp75 (TRP-1), tyrosinase, NY-ESO-1, melanoma proteoglycan, a MAGE family antigen, a BAGE family antigen, a GAGE family antigen, a RAGE family antigens, N-acetylglucosaminyltransferase-V, p15, β

-catenin, MUM-1, cyclin dependent kinase-4 (CDK4), p21-ras, BCR-abl, p53, p185 (HER2/neu), epidermal growth factor receptor (EGFR), carcinoembryonic antigen (CEA), a carcinoma-associated mutated mucin, MUC-1, prostate specific antigen (PSA), prostate specific membrane antigen (PSMA), KSA, kinesin 2, HIP-55, TGFβ

-1 anti-apoptotic factor, tumor protein D52, H1FT, NY-BR-1, NY-BR-62, NY-BR-75, NY-BR-85, NY-BR- 87, NY-BR-96, and a pancreatic cancer antigen.

14. A composition comprising the recombinant NYVAC vector of claim 4 and a pharmaceutically acceptable carrier.

15. A method of inducing an immune response in a host against a viral target antigen, a bacterial target antigen, a parasitic target antigen, or a tumor target antigen comprising administering an effective amount of the composition of claim 14 to the host.

16. The method of claim 15, for inducing am immune response in a host against human immunodeficiency virus (HIV) wherein the vector encodes an immunogen derived from HIV and administering to the host a peptide selected from the group consisting of ENV, GAG, POL, NET, VGNLWVTVYYGVPVW (SEQ ID NO. 31), WVTVYYGVPVWKGAT (SEQ ID NO. 32), GATTTLFCASDAKAY (SEQ ID NO. 33), TTLFCASDAKAYDTE (SEQ ID NO. 34), THACVPADPNPQEMV (SEQ ID NO. 35), ENVTENFNMWKNEMV (SEQ ID NO. 36), ENFNMWKNEMVNQMQ (SEQ ID NO. 37), EMVNQMQEDVISLWD (SEQ ID NO. 38), CVKLTPLCVTLECRN (SEQ ID NO. 39), NCSFNATTVVRDRKQ (SEQ ID NO. 40), NATTVVRDRKQTVYA (SEQ ID NO. 41), VYALFYRLDIVPLTK (SEQ ID NO. 42), FYRLDIVPLTKKNYS (SEQ ID NO. 43), INCNTSAITQACPKV (SEQ ID NO. 44), PKVTFDPIPIHYCTP (SEQ ID NO. 45), FDPIPIHYCTPAGYA (SEQ ID NO. 46), TGDIIGDIRQAHCNI (SEQ ID NO. 47), SSSIITIPCRIKQII (SEQ ID NO. 48), ITIPCRIKQIINMWQ (SEQ ID NO. 49), CRIKQIINMWQEVGR (SEQ ID NO. 50), VGRAMYAPPIKGNIT (SEQ ID NO. 51), MYAPPIKGNITCKSN (SEQ II) NO. 52), PIKGNITCKSNITGL (SEQ ID NO. 53), ETFRPGGGDMRNNWR (SEQ ID NO. 54), ELYKYKVVEIKPLGV (SEQ ID NO. 55), YKVVEIKPLGVAPTT (SEQ ID NO. 56), EIKPLGVAPTTTKRR (SEQ ID NO. 57), LGVAPTTTKRRVVER (SEQ ID NO. 58), and YSENSSEYY (SEQ ID NO. 59).

17. The method of claim 15, wherein the host is a human being.