Vectors for molecule delivery to CD11b expressing cells

Abstract

The invention relates to a novel use of a Bordetella adenylcyclase toxin in the manufacturing of vectors for targeting in vivo a molecule of interest, specifically to CD11b expressing cells. The invention also relates to an immunogenic composition that primes immune responses, to pharmaceutical compositions and to a new vector for molecule delivery to CD11b expressing cells.

What is claimed is:  
     
         1 . Use of Bordetella species adenylcyclase in the manufacturing of a proteinaceous vector for targeting a molecule of interest specifically to CD11b expressing cells.  
     
     
         2 . Use of a Bordetella adenylcyclase wherein said adenylcyclase is modified by insertion of a molecule of interest for the preparation of a composition for the targeting of said molecule to CD11b expressing cells.  
     
     
         3 . The use according to  claim 2  wherein said Bordetella species adenylcyclase is a fragment of the Bordetella adenylcyclase toxin, wherein said fragment is capable of binding the CD1 b receptor.  
     
     
         4 . The use according to  claim 3 , wherein said fragment of the Bordetella adenylcyclase toxin capable of binding the CD11b receptor is the Bordetella adenylcyclase toxin lacking all or part of its N-terminal catalytic domain.  
     
     
         5 . The use according to  claim 4 , wherein said fragment of the Bordetella adenylcyclase toxin capable of binding the CD11b receptor is the  Bordetella pertussis  adenylcyclase toxin lacking all or part of residues 1-373.  
     
     
         6 . The use according to anyone of  claims 1  to  5  wherein the targeting of said molecule of interest is effective in vivo.  
     
     
         7 . The use according to any one of  claims 1  to  6  wherein the molecule of interest is specifically targeted and translocated in the cytosol of CD11b expressing cells.  
     
     
         8 . The use according to any one of  claims 1  to  7  wherein said CD11b expressing cells are dendritic cells and more preferably myeloid dendritic cells.  
     
     
         9 . The use according to any one of  claims 1  to  8  wherein said CD11b expressing cells are neutrophils.  
     
     
         10 . The use according to any one of  claims 1  to  9  wherein the adenylcyclase is a genetically modified Bordetella species adenylcyclase.  
     
     
         11 . The use according to any one of  claims 1  to  10  wherein the adenylcyclase is a non toxic form.  
     
     
         12 . The use according to any one of  claims 1  to  11  wherein the adenylcyclase is from Bordetella pertussis.  
     
     
         13 . The use according to any one of  claims 1  to  12  wherein the molecule of interest is selected in the group comprising: peptides, glycopeptides, lipopeptides, polysaccharides, oligosaccharides, nucleic acids, lipids and chemicals.  
     
     
         14 . The use according to  claim 13  wherein the molecule of interest is an antigen.  
     
     
         15 . The use according to  claim 13  wherein the molecule of interest comprises an epitope.  
     
     
         16 . The use according to  claim 15 , wherein the molecule of interest is a heterologous peptide fused to the N-terminal extremity of a genetically modified Bordetella adenylcyclase lacking all or part of its N-terminal catalytic domain, and more preferably  Bordetella pertussis  adenylcyclase lacking residues 1-373.  
     
     
         17 . The use according to  claim 14  wherein said antigen is selected from the group consisting of an intracellular bacterial cell antigen, a tumoral cell antigen, a viral antigen, a fungus antigen or a parasite cell antigen.  
     
     
         18 . The use according to  claim 17  wherein said antigen is selected from the group consisting of: a poliovirus antigen, an HIV virus antigen, an influenza virus antigen, a choriomeningitis virus epitope, a tumor antigen.  
     
     
         19 . The use according to any one of  claims 1  to  13  wherein the molecule of interest is a drug chemically or genetically coupled to the adenylcyclase toxin.  
     
     
         20 . The use according to  claim 19 , wherein said drug is chemically coupled by means of a disulfide bond to a genetically inserted cysteine residue located in the catalytic domain of said adenylcyclase.  
     
     
         21 . The use according to any one of  claim 19  or  20 , wherein the drug is an anti-inflammatory drug.  
     
     
         22 . An immunogenic composition formulated for administration in an animal or a human host characterized in that it comprises a Bordetella adenylcyclase which comprises an antigen inserted in the catalytic domain.  
     
     
         23 . A pharmaceutical composition for administration in a human or an animal formulated for targeting a molecule of interest specifically to CD11b expressing cells characterized in that said molecule of interest is coupled to a Bordetella species adenylcyclase.  
     
     
         24 . The immunogenic or pharmaceutical composition according to  claim 22  or  23 , wherein the adenylcyclase is a genetically modified adenylcyclase.  
     
     
         25 . The immunogenic or pharmaceutical composition according to  claim 24 , wherein the genetically modified adenylcyclase is able to translocate the molecule of interest specifically in the cytosol of CD11 b expressing cells.  
     
     
         26 . The immunogenic or pharmaceutical composition according to  claim 25 , wherein said genetically modified adenylcyclase is a Bordetella adenylcyclase lacking all or part of its catalytic N-terminal domain.  
     
     
         27 . The immunogenic or pharmaceutical composition according to  claim 25 , wherein said genetically modified adenylcyclase is the  Bordetella pertussis  adenylcyclase lacking residues 1-373.  
     
     
         28 . The immunogenic or pharmaceutical composition according to any one of  claim 24  or  25 , wherein said genetically modified adenylcyclase comprises one or more cysteine residue(s) inserted within the catalytic domain at a permissive site.  
     
     
         29 . The immunogenic or pharmaceutical composition according to any one of  claims 22  to  28 , wherein said CD11b expressing cells are dendritic cells and more preferably myeloid dendritic cells.  
     
     
         30 . The immunogenic or pharmaceutical composition according to any one of  claims 22  to  28 , wherein said CD11b expressing cells are neutrophils.  
     
     
         31 . The pharmaceutical or immunogenic composition according to  claims 22  to  30 , wherein the molecule of interest is selected in the group comprising: peptides, glycopeptides, lipopeptides, polysaccharides, oligosaccharides, nucleic acids, lipids and chemicals.  
     
     
         32 . The pharmaceutical or immunogenic composition according to  claims 22  to  29 , wherein said composition comprises a nucleic acid construction encoding the Bordetella species adenylate cyclase coupled to a molecule of interest.  
     
     
         33 . The pharmaceutical or immunogenic composition according to  claim 31 , wherein the molecule of interest is a drug.  
     
     
         34 . The pharmaceutical composition according to  claim 33 , wherein the drug is an anti-inflammatory drug.  
     
     
         35 . The pharmaceutical or immunogenic composition according to  claims 22  to  31 , wherein the molecule of interest is an antigen.  
     
     
         36 . The immunogenic or pharmaceutical composition according to  claim 35  wherein the antigen is selected from the group consisting of: an intracellular bacterial cell antigen, a tumoral cell antigen, a viral antigen, a fungus antigen or a parasite cell antigen.  
     
     
         37 . The immunogenic or pharmaceutical composition according to  claim 36  wherein the antigen is selected from the group consisting of; a poliovirus antigen, an HIV virus, an influenza virus antigen, a choriomeningitis virus antigen, a tumor antigen.  
     
     
         38 . The immunogenic or pharmaceutical composition according to any one of  claims 35  to  37 , wherein said antigen is fused to the N-terminal part of a genetically modified Bordetella adenylcyclase lacking its N-terminal catalytic domain.  
     
     
         39 . The immunogenic or pharmaceutical composition according to any one of  claims 35  to  38 , wherein said antigen is fused to the genetically modified  Bordetella pertussis  adenylcyclase lacking residues 1-373.  
     
     
         40 . The immunogenic or pharmaceutical composition according to any one of  claims 22  to  39  wherein said composition is formulated for intravenous administration and especially is devoid of priming adjuvants.  
     
     
         41 . The immunogenic composition according to any one of  claims 22  to  40 , wherein said immunogenic composition is capable of inducing or stimulating an immune response involving specifically dendritic cells.  
     
     
         42 . Use of the immunogenic or pharmaceutical composition according to any one of  claims 35  to  39  for the preparation of a vaccine or an immunotherapeutic composition.  
     
     
         43 . A proteinaceous vector for delivery of a molecule of interest, specifically to CD11b expressing cells, characterized in that said vector comprises a recombinant Bordetella species adenylcyclase coupled to said molecule of interest.  
     
     
         44 . The proteinaceous vector according to  claim 43  wherein said vector is also able to deliver the molecule of interest specifically in the cytosol of CD11b expressing cells.  
     
     
         45 . The proteinaceous vector according to  claim 43  or  44  wherein said CD11b expressing cells are dendritic cells and more preferably myeloid dendritic cells.  
     
     
         46 . The proteinaceous vector according to  claim 43  or  44  wherein said CD11b expressing cells are neutrophils.  
     
     
         47 . The proteinaceous vector according to any one of  claims 43  to  46  wherein the adenylcyclase is a genetically modified adenylcyclase.  
     
     
         48 . The proteinaceous vector according to  claim 47 , wherein said genetically modified adenylcyclase is devoid of native cysteine residue but contains genetically inserted cysteine residue(s) at permissive site(s) within the catalytic domain.  
     
     
         49 . The proteinaceous vector according to any one of  claim 47  or  48  wherein the adenylcyclase is a non toxic adenylcyclase.  
     
     
         50 . The proteinaceous vector according to any one of  claims 47  to  49 , wherein the genetically modified adenylcyclase is a Bordetella adenylclase lacking all or part of its N-terminal catalytic domain.  
     
     
         51 . The proteinaceous vector according to any one of  claims 43  to  50  wherein the adenylcyclase is from  Bordetella pertussis.    
     
     
         52 . The proteinaceous vector according to  claim 51 , wherein said recombinant adenylcyclase is the  Bordetella pertussis  adenylcyclase lacking residues 1-373.  
     
     
         53 . The proteinaceous vector according to  claims 43  to  52 , wherein said molecule of interest is selected in the group comprising: peptides, glycopeptides, lipopeptides, polysaccharides, oligosaccharides, nucleic acids, lipids and chemicals.  
     
     
         54 . The proteinaceous vector according to any one of  claims 43  to  53 , wherein said molecule of interest is a drug chemically or genetically coupled to said adenylcyclase.  
     
     
         55 . The proteinaceous vector according to  claim 54 , wherein the molecule of interest is an epitope.  
     
     
         56 . The proteinaceous vector according to any one of  claim 54  or  55 , wherein said molecule of interest is an epitope chemically coupled to a genetically modified adenylcyclase devoid of native cysteine residue but containing genetically inserted cysteine residue(s) at permissive site(s) within its catalytic domain.