Modified Vaccinia virus Ankara for the vaccination of neonates

Abstract

The invention concern the use of a virus for the preparation of a medicament for the vaccination or treatment of a neonatal or prenatal animal, including a human, wherein the virus is capable of infecting the cells of the neonatal or prenatal animal, including a human, but not capable of being replicated to infectious progeny virus in the neonatal or prenatal animal, including a human. The virus is preferably a Modified Vaccinia Virus Ankara. In particular, the invention concerns the vaccination of neonates against infections with viruses belonging to the same virus group than the virus used for vaccination. Moreover, the invention concerns the vaccination of neonates against antigens selected from foreign antigens and tumour antigens, wherein the tumour antigen and/or the foreign antigen are different from the antigens associated with the virus. The invention further concerns the use of viruses as defined above to increase the level of factors which activate dendritic cells or their precursor cells and/or to increase the number of dendritic cells or their precursor cells and/or to increase the production and/or cellular content of an interferon (IFN) or IL-12.

1 . An MVA virus characterized by 
 (i) being capable of reproductive replication in vitro in chicken embryo fibroblasts (CEF) and by being non-replicative in vitro in human cells, and    (ii) by a failure to replicate in a mouse strain that is incapable of producing mature B and T cells and as such is severely immune compromised and highly susceptible to a replicating virus, for administration to induce a general immune stimulation in an animal, including a human, in need thereof.    
   
   
       2 . The MVA virus of  claim 1 , wherein the human cells are the human keratinocyte cell line HaCaT, the human embryo kidney cell line 293, the human bone osteosarcoma cell line (143 B), and the human cervix adenocarcinoma cell line HeLa.  
   
   
       3 . The MVA virus of  claim 1 , which is MVA-BN deposited at the European Collection of Cell Cultures (ECACC), Salisbury (UK) under number V00083008 or derivatives thereof exhibiting the same replication characteristics.  
   
   
       4 . The MVA virus of  claim 1 , wherein administration to the animal, including the human, in need of general immune stimulation, increases (i) the level of factors which activate and/or mobilize dendritic cells or their precursor cells, (ii) the number of dendritic cells or their precursor cells, and/or (iii) the production and/or cellular content of an interferon (IFN) or IL-12.  
   
   
       5 . The MVA virus of  claim 1 , wherein the general immune stimulation is characterized by stimulating a cell-mediated immune response.  
   
   
       6 . The MVA virus of  claim 1 , wherein the general immune stimulation is characterized by an increase in the number of dendritic cells and their precursor cells.  
   
   
       7 . The MVA virus of  claim 6 , wherein the precursors of dendritic cells are plasmacytoid dendritic cell precursors.  
   
   
       8 . The MVA virus of  claim 1 , wherein the general immune stimulation is characterized as an increase in the number of T lymphocytes.  
   
   
       9 . The MVA virus of  claim 8 , wherein the T lymphocytes comprise CD8+T cells and/or CD4+T helper cells.  
   
   
       10 . The MVA virus of  claim 1 , wherein the general immune stimulation is characterized by an at least 1.5 fold increase in the concentration of Flt3-L two days after administration of the virus.  
   
   
       11 . The MVA virus of  claim 1 , wherein the animal, including the human, in need of general immune stimulation is receiving antiviral therapy.  
   
   
       12 . The MVA virus of  claim 11 , wherein the antiviral therapy is for the treatment of a virus belonging to the family Retroviridae.  
   
   
       13 . The MVA virus of  claim 12 , wherein the virus belonging to the family Retroviridae is selected from HIV-1, HIV-2, SIV, Simian-Human immunodeficiency virus, Feline immunodeficiency virus, Bovine immunodeficiency virus and Equine immunodeficiency virus.  
   
   
       14 . The MVA virus of  claim 11 , wherein the antiviral therapy eliminates and/or suppresses a viral infection.  
   
   
       15 . The MVA virus of  claim 11 , wherein the antiviral therapy includes administration of nucleoside analogs, inhibitors of viral enzymatic activity, inhibitors of viral assembly, cytokines and/or a combination thereof.  
   
   
       16 . The MVA virus of  claim 12 , wherein the antiviral therapy is highly active antiretroviral therapy (HAART).  
   
   
       17 . The MVA virus of  claim 1 , wherein the animal in need of general immune stimulation is a human with an HIV-induced immune deficiency.  
   
   
       18 . The MVA virus of  claim 1 , wherein the animal, including the human, in need of general immune stimulation, has a condition linked to low CD4+levels selected from breast cancer, chronic lymphatic leukaemia (CLL), HIV infection, HIV infection with an opportunistic infection, Kaposi's sarcoma, and chemotherapy-induced lymphopenia.  
   
   
       19 . A method of inducing a general immune stimulation in an animal, including a human, in need of general immune stimulation, comprising the step of administering to the animal, including the human, an effective amount of the MVA virus of  claim 1 .  
   
   
       20 . The method of  claim 19 , wherein the MVA virus is administered by oral, nasal, intramuscular, intravenous, intraperitoneal, intradermal, intra-utero and/or subcutaneous application.  
   
   
       21 . The method of  claim 19 , wherein the MVA virus is administered to the animal, including the human, in need of general immune stimulation in an amount of at least 1 01 TCID 50  (tissue culture infectious dose).  
   
   
       22 . The method of  claim 19 , wherein administration to the animal, including the human, in need of general immune stimulation, increases (i) the level of factors which activate and/or mobilize dendritic cells or their precursor cells, 
 (ii) the number of dendritic cells or their precursor cells, and/or (iii) the production and/or cellular content of an interferon (IFN) or IL-12.    
   
   
       23 . The method of  claim 19 , wherein the general immune stimulation is characterized by stimulating a cell-mediated immune response.  
   
   
       24 . The method of  claim 19 , wherein the general immune stimulation is characterized by an increase in the number of dendritic cells and their precursor cells.  
   
   
       25 . The method of  claim 24 , wherein the precursors of dendritic cells are plasmacytoid dendritic cell precursors.  
   
   
       26 . The method of  claim 19 , wherein the general immune stimulation is characterized by an at least 1.5 fold increase in the concentration of Flt3-L two days after administration of the virus.  
   
   
       27 . The method of  claim 19 , wherein the general immune stimulation is characterized as an increase in the number of T lymphocytes.  
   
   
       28 . The method of  claim 27 , wherein the T lymphocytes comprise CD8+T cells and/or CD4+T helper cells  
   
   
       29 . The method of  claim 19 , wherein the animal, including the human, is receiving antiviral therapy.  
   
   
       30 . The method of  claim 29 , wherein the antiviral therapy is for the treatment of a virus belonging to the family Retroviridae.  
   
   
       31 . The method of  claim 30 , wherein the virus belonging to the family Retroviridae is selected from HIV-1, HIV-2, SIV, Simian-Human immunodeficiency virus, Feline immunodeficiency virus, Bovine immunodeficiency virus and Equine immunodeficiency virus.  
   
   
       32 . The method of  claim 29 , wherein the antiviral therapy eliminates and/or suppresses a viral infection.  
   
   
       33 . The method of  claim 29 , wherein the antiviral therapy includes administration of nucleoside analogs, inhibitors of viral enzymatic activity, inhibitors of viral assembly, cytokines, and/or a combination thereof.  
   
   
       34 . The method of  claim 30 , wherein the antiviral therapy is highly active antiretroviral therapy (HAART).  
   
   
       35 . The method of  claim 19 , wherein the animal in need of general immune stimulation is a human with an HIV-induced immune deficiency.  
   
   
       36 . The method of  claim 19 , wherein the animal, including the human, in need of general immune stimulation, has a condition linked to low CD4+levels selected from breast cancer, chronic lymphatic leukaemia (CLL), HIV infection, HIV infection with an opportunistic infection, Kaposi's sarcoma, and chemotherapy-induced lymphopenia.  
   
   
       37 . A method of inducing a general immune stimulation in an animal, including a human, in need of general immune stimulation, comprising the step of administering to the animal, including the human, an effective amount of an MVA strain, wherein the general immune stimulation is characterized as an increase in the number of T lymphocytes.  
   
   
       38 . The method of  claim 37 , wherein the MVA strain is selected from MVA-575 (ECACC V00120707), MVA-572 (ECACC V94012707) and the MVA virus of  claim 1 .  
   
   
       39 . The method of  claim 37 , wherein the T lymphocytes comprise CD8+T cells and/or CD4+T helper cells.  
   
   
       40 . The method of  claim 37 , wherein the animal, including the human, is receiving antiviral therapy.  
   
   
       41 . The method of  claim 40 , wherein the antiviral therapy is for the treatment of a virus belonging to the family Retroviridae.  
   
   
       42 . The method of  claim 41 , wherein the virus belonging to the family Retroviridae is selected from HIV-1, HIV-2, SIV, Simian-Human immunodeficiency virus, Feline immunodeficiency virus, Bovine immunodeficiency virus and Equine immunodeficiency virus.  
   
   
       43 . The method of  claim 40 , wherein the antiviral therapy eliminates and/or suppresses a viral infection.  
   
   
       44 . The method of  claim 40 , wherein the antiviral therapy includes administration of nucleoside analogs, inhibitors of viral enzymatic activity, inhibitors of viral assembly, cytokines, and/or a combination thereof.  
   
   
       45 . The method of  claim 41 , wherein the antiviral therapy is highly active antiretroviral therapy (HAART).  
   
   
       46 . The method of  claim 37 , wherein the animal in need of general immune stimulation is a human with an HIV-induced immune deficiency.  
   
   
       47 . The method of  claim 37 , wherein the animal, including the human, in need of general immune stimulation, has a condition linked to low CD4+levels selected from breast cancer, chronic lymphatic leukaemia (CLL), HIV infection, HIV infection with an opportunistic infection, Kaposi's sarcoma, and chemotherapy-induced lymphopenia.