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.

1 - 56 . (canceled)  
     
     
         57 . The method of modifying CD11b expressing cells, wherein the method comprises targeting a molecule of interest to the cells by contacting a  Bordetella  adenylcyclase with cells, wherein the  Bordetella  adenylcyclase comprises the molecule of interest.  
     
     
         58 . The method of  claim 57 , wherein the targeting of the molecule of interest is effective in vivo.  
     
     
         59 . The method of  claim 57 , wherein the molecule of interest is translocated to the cytosol of the CD11b expressing cells.  
     
     
         60 . The method of  claim 57 , wherein the CD11b expressing cells comprises dendritic cells.  
     
     
         61 . The method of  claim 57 , wherein the CD11b expressing cells comprises myeloid dendritic cells.  
     
     
         62 . The method of  claim 57 , wherein the CD11b expressing cells comprise neutrophils.  
     
     
         63 . The method of  claim 57 , wherein the adenylcyclase comprises a genetically modified  Bordetella  species adenylcyclase.  
     
     
         64 . The method of  claim 57 , wherein the adenylcyclase comprises a non-toxic form.  
     
     
         65 . The method of  claim 57 , wherein the adenylcyclase comprises a  Bordetella pertussis  adenylcyclase.  
     
     
         66 . The method of  claim 57 , wherein the molecule of interest is selected from peptides, glycopeptides, lipopeptides, polysaccharides, oligosaccharides, nucleic acids, lipids, and chemicals.  
     
     
         67 . The method of  claim 66 , wherein the molecule of interest comprises an antigen.  
     
     
         68 . The method of  claim 66 , wherein the molecule of interest comprises an epitope.  
     
     
         69 . The method of  claim 66 , wherein the molecule of interest comprises 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.  
     
     
         70 . The method of  claim 69 , wherein the molecule of interest comprises a heterologous peptide fused to the N-terminal extremity of a genetically modified  Bordetella pertussis  adenylcyclase lacking residues 1-373.  
     
     
         71 . The method of  claim 67 , wherein said antigen is selected from an intracellular bacterial cell antigen, a tumoral cell antigen, a viral antigen, a fungus antigen, and a parasite cell antigen.  
     
     
         72 . The method of  claim 71 , wherein said antigen is selected from a poliovirus antigen, an HIV antigen, an influenza virus antigen, a choriomeningitis virus epitope, and a tumor antigen.  
     
     
         73 . The method of  claim 57 , wherein the molecule of interest comprises a drug chemically or genetically coupled to the adenylcyclase toxin.  
     
     
         74 . The method of  claim 73 , wherein the drug is chemically coupled by a disulfide bond to a genetically inserted cysteine residue located in a catalytic domain of the adenylcyclase.  
     
     
         75 . The method of  claim 74 , wherein the adenylcyclase is a  Bordetella pertussis  adenylcyclase, and wherein the cysteine residue is inserted at a site selected from residues 137-138, 224-225, 228-229, 235-236, 317-318, and 335-336.  
     
     
         76 . The method of any one of claims  73 - 75 , wherein the drug is an anti-inflammatory drug.  
     
     
         77 . The method of  claim 57 , wherein the adenylcyclase comprises the molecule of interest in its catalytic domain.  
     
     
         78 . The method of  claim 77 , wherein the molecule of interest is inserted at a permissive site within the catalytic domain.  
     
     
         79 . The method of  claim 78 , wherein the adenylcyclase comprises a  Bordetella pertussis  adenylclase, and wherein the catalytic domain comprises amino acids 1-400.  
     
     
         80 . A method of modifying CD11b expressing cells, wherein the method comprises targeting a molecule of interest to the cells by administering to a mammal a  Bordetella  adenylcyclase, wherein the  Bordetella  adenylcyclase comprises the molecule of interest.  
     
     
         81 . The method of  claim 80 , wherein the CD11b expressing cells comprise myeloid dendritic cells.  
     
     
         82 . The method of  claim 80 , wherein the adenylcyclase is a  Bordetella pertussis  adenylcyclase  
     
     
         83 . The method of  claim 80 , wherein the molecule of interest comprises a drug chemically coupled to the adenylcyclase toxin by a disulfinde bond to a genetically inserted cysteine residue inserted at a site selected from residues 137-138, 224-225, 228-229, 235-236, 317-318, and 335-336.  
     
     
         84 . The method of  claim 80 , wherein the CD11b expressing cells comprise myeloid dendritic cells, wherein the adenylcyclase is a  Bordetella pertussis  adenylcyclase, wherein the molecule of interest comprises a drug chemically coupled to the adenylcyclase toxin by a disulfinde bond to a genetically inserted cysteine residue inserted at a site selected from residues 137-138, 224-225, 228-229, 235-236, 317-318, and 335-336.