Lectin compositions and methods for modulating an immune response to an antigen

Abstract

The present invention provides a fusion polypeptide which can bind to a cell surface binding moiety (e.g., a carbohydrate) and serve as a ligand for a cell surface polypeptide, as well as a vector comprising a nucleic acid encoding for such a fusion polypeptide, and a host cell comprising such nucleic acid. The present invention also provides a composition comprising an antigen bearing target and such a fusion polypeptide, as well as a composition comprising a virus or a cell and such a fusion polypeptide. The present invention further relates to a method of modulating an immune response in an animal using such compositions.

1 . A vaccine composition comprising an antigen bearing target and further comprising a fusion polypeptide, said fusion polypeptide comprising 
 a first amino acid sequence which can bind to a carbohydrate and    a second amino acid sequence comprising a ligand for a cell surface polypeptide, said ligand being chosen from the group: a ligand for a cytokine receptor, a ligand for CD40, a ligand for an adhesion molecule, a ligand for a defensin receptor, a ligand for a heat shock protein receptor, a ligand for a T cell costimulatory molecule, a ligand for a counterreceptor for a T cell costimulatory molecule.    
     
     
         2 . The vaccine composition of  claim 1 , wherein said antigen bearing target comprises at least one of the following: a tumor antigen, a viral antigen, a bacterial antigen, a fungal antigen, a parasite antigen, a prion antigen, an antigen of an autoimmune disease.  
     
     
         3 . The vaccine composition of  claim 1 , wherein said antigen bearing target is chosen from the group: a tumor cell, a virus, a bacterial cell, a fungal cell, a cell of a parasite, a prion, a mammalian cell, an insect cell, a polypeptide free of other cell-derived material.  
     
     
         4 . The vaccine composition of  claim 2 , wherein said antigen bearing target is pathogenic.  
     
     
         5 . The vaccine composition of  claim 2 , wherein said antigen bearing target is attenuated.  
     
     
         6 . The vaccine composition of  claim 1 , wherein said antigen bearing target is a cell which is substantially unable to divide.  
     
     
         7 . The vaccine composition of  claim 2 , wherein said antigen bearing target is a cell and said fusion polypeptide is exogenous to said cell.  
     
     
         8 . The vaccine composition of  claim 2 , wherein said antigen bearing target is a cell and said fusion polypeptide is endogenous to said cell and is encoded by a nucleic acid sequence comprised by the cell.  
     
     
         9 . The vaccine composition of  claim 1 , wherein said first amino acid sequence is N-terminal to said second amino acid sequence.  
     
     
         10 . The vaccine composition of  claim 1 , wherein said first amino acid sequence is C-terminal to said second amino acid sequence.  
     
     
         11 . The vaccine composition of  claim 1 , wherein said first amino acid sequence can bind to a sialic acid on a glycoprotein, said sialic acid comprising at least one of the following carbohydrate structures: N-acetylneuraminic acid, alpha-NeuNAc-[2->6]-Gal, alpha-NeuNAc-[2->6]-GalNAc, alpha-NeuNAc-[2->3]-Gal.  
     
     
         12 . The vaccine composition of  claim 1 , wherein said first amino acid sequence comprises a carbohydrate-binding domain of a naturally occuring lectin.  
     
     
         13 . The vaccine composition of  claim 1 , wherein said first amino acid sequence comprises at least about 10 contiguous amino acids of a hemagglutinin.  
     
     
         14 . The vaccine composition of  claim 12 , wherein said hemagglutinin is an influenza virus hemagglutinin.  
     
     
         15 . The vaccine composition of  claim 13 , wherein said contiguous amino acids of an influenza hemagglutinin are contiguous amino acids of an influenza hemagglutinin HA1 domain.  
     
     
         16 . The vaccine composition of  claim 14 , wherein said influenza virus is an influenza A virus.  
     
     
         17 . The vaccine composition of  claim 15 , wherein said influenza virus is of a subtype that infects humans.  
     
     
         18 . The vaccine composition of  claim 15 , wherein said influenza virus is of an H1 subtype.  
     
     
         19 . The vaccine composition of  claim 17 , wherein said influenza virus is from the strain A/PR/8/34.  
     
     
         20 . The vaccine composition of  claim 15 , wherein said influenza virus is of an H2 or H3 subtype.  
     
     
         21 . The vaccine composition of  claim 15 , wherein said influenza virus is of a subtype that does not infect humans.  
     
     
         22 . The vaccine composition of  claim 1 , wherein said ligand for a cell surface polypeptide is a ligand for a mammalian cell surface polypeptide.  
     
     
         23 . The vaccine composition of  claim 21 , wherein said ligand for a cell surface polypeptide is a ligand for a mouse cell surface polypeptide.  
     
     
         24 . The vaccine composition of  claim 21 , wherein said ligand for a cell surface polypeptide is a ligand for a human cell surface polypeptide.  
     
     
         25 . The vaccine composition of  claim 1 , wherein said ligand for a cell surface polypeptide is a ligand for a cell surface polypeptide of a leukocyte.  
     
     
         26 . The vaccine composition of  claim 1 , wherein said ligand for a cell surface polypeptide is a ligand for a cell surface polypeptide of an antigen presenting cell.  
     
     
         27 . The vaccine composition of  claim 26 , wherein said ligand for a cell surface polypeptide is a ligand for a cell surface polypeptide of a professional antigen presenting cell.  
     
     
         28 . The vaccine composition of  claim 1 , wherein said ligand for a cell surface polypeptide is a ligand for a cell surface polypeptide of a dendritic cell.  
     
     
         29 . The vaccine composition of  claim 1 , wherein said ligand for a cell surface polypeptide is a ligand for a mouse GM-CSF receptor.  
     
     
         30 . The vaccine composition of  claim 1 , wherein said ligand for a cell surface polypeptide comprises at least about five contiguous amino acids of a mouse GM-CSF.  
     
     
         31 . The vaccine composition of  claim 1 , wherein said ligand for a cell surface polypeptide comprises a mouse GM-CSF.  
     
     
         32 . The vaccine composition of  claim 1 , wherein said ligand for a cell surface polypeptide is a ligand for a human GM-CSF receptor.  
     
     
         33 . The vaccine composition of  claim 1 , wherein said ligand for a cell surface polypeptide comprises at least about five contiguous amino acids of a human GM-CSF.  
     
     
         34 . The vaccine composition of  claim 1 , wherein said ligand for a cell surface polypeptide comprises a human GM-CSF.  
     
     
         35 . The vaccine composition of  claim 1 , wherein said ligand for a cell surface polypeptide is a ligand for a receptor for an interleukin.  
     
     
         36 . The vaccine composition of  claim 1 , wherein said ligand for a cell surface polypeptide is a ligand for a receptor for a mouse interleukin.  
     
     
         37 . The vaccine composition of  claim 1 , wherein said ligand for a cell surface polypeptide is a ligand for a receptor for a human interleukin.  
     
     
         38 . The vaccine composition of  claim 35 , wherein said interleukin is chosen from the group: IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-1, IL-12, IL-13, IL-14, IL-15, IL-16, IL-17, IL-18, IL-19, IL-20, IL-21, IL-22, IL-23, IL-24, IL-25.  
     
     
         39 . The vaccine composition of  claim 1 , wherein said ligand for a cell surface polypeptide comprises at least about 5 contiguous amino acids of an interleukin.  
     
     
         40 . The vaccine composition of  claim 39  wherein said interleukin is chosen from the group: IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-1, IL-12, IL-13, IL-14, IL-15, IL-16, IL-17, IL-18, IL-19, IL-20, IL-21, IL-22, IL-23, IL-24, IL-25.  
     
     
         41 . The vaccine composition of  claim 1 , wherein said ligand for a cell surface polypeptide comprises an interleukin.  
     
     
         42 . The vaccine composition of  claim 41  wherein said interleukin is chosen from the group: IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12, IL-13, IL-14, IL-15, IL-16, IL-17, IL-18, IL-19, IL-20, IL-21, IL-22, IL-23, IL-24, IL-25.  
     
     
         43 . The vaccine composition of  claim 1 , wherein said ligand for a cell surface polypeptide is a ligand for a receptor for a chemokine.  
     
     
         44 . The vaccine composition of  claim 1 , wherein said ligand for a cell surface polypeptide is a ligand for a receptor for a mouse chemokine.  
     
     
         45 . The vaccine composition of  claim 1 , wherein said ligand for a cell surface polypeptide is a ligand for a receptor for a human chemokine.  
     
     
         46 . The vaccine composition of  claim 43 , wherein said chemokine is a C-C cytokine.  
     
     
         47 . The vaccine composition of  claim 43 , wherein said chemokine is a C-X-C cytokine.  
     
     
         48 . The vaccine composition of  claim 43 , wherein said cell surface polypeptide is chosen from the group: CXCR-1, CXCR-2, CXCR-3, CXCR-4, CCR-1, CCR-2, CCR-3, CCR-4, CCR-5, CCR-6, CCR-7, CCR-8.  
     
     
         49 . The vaccine composition of  claim 43 , wherein said chemokine is chosen from the group: 9E3, AMCF, beta-thromboglobulin, ENA-78, eotaxin, eotaxin-2, IP-10, KC, LIX, mig, MGSA, mob-1, NAP-2, NAP-3, NAP-4, PBSF, MGSA, mouse KC, MIP-2, MIP-1 alpha, NAP-2, ENA-78, GCP-2, ACT-2, C10, CCF18, DC-CK1, ELC, Exodus, FIC, GDCF, GDCF-2, HC-21, HCC-1,1-309, JE, LAG-1, MARC, MCAF, MCP-1, MCP-2, MCP-3, MCP-4, MCP-5, MRP-2, RANTES SDF, TARC, ATAC, Ltn, SCM-1, neurotactin.  
     
     
         50 . The vaccine composition of  claim 43 , wherein said ligand for a cell surface polypeptide comprises at least about 5 contiguous amino acids of a chemokine.  
     
     
         51 . The vaccine composition of  claim 50 , wherein said chemokine is chosen from the group: 9E3, AMCF, beta-thromboglobulin, ENA-78, eotaxin, eotaxin-2, IP-10, KC, LIX, mig, MGSA, mob-1, NAP-2, NAP-3, NAP-4, PBSF, MGSA, mouse KC, MIP-2, MIP-1 alpha, NAP-2, ENA-78, GCP-2, ACT-2, C10, CCF18, DC-CK1, ELC, Exodus, FIC, GDCF, GDCF-2, HC-21, HCC-1,1-309, JE, LAG-1, MARC, MCAF, MCP-1, MCP-2, MCP-3, MCP-4, MCP-5, MRP-2, RANTES SDF, TARC, ATAC, Ltn, SCM-1, neurotactin.  
     
     
         52 . The vaccine composition of  claim 1 , wherein said ligand for a cell surface polypeptide comprises a chemokine.  
     
     
         53 . The vaccine composition of  claim 52  wherein said chemokine is chosen from the group: 9E3, AMCF, beta-thromboglobulin, ENA-78, eotaxin, eotaxin-2, IP-10, KC, LIX, mig, MGSA, mob-1, NAP-2, NAP-3, NAP-4, PBSF, MGSA, mouse KC, MIP-2, MIP-1 alpha, NAP-2, ENA-78, GCP-2, ACT-2, C10, CCF18, DC-CK1, ELC, Exodus, FIC, GDCF, GDCF-2, HC-21, HCC-1,1-309, JE, LAG-1, MARC, MCAF, MCP-1, MCP-2, MCP-3, MCP-4, MCP-5, MRP-2, RANTES SDF, TARC, ATAC, Ltn, SCM-1, neurotactin.  
     
     
         54 . The vaccine composition of  claim 1 , wherein said ligand for a cell surface polypeptide is a ligand for a receptor for an interferon.  
     
     
         55 . The vaccine composition of  claim 1 , wherein said ligand for a cell surface polypeptide is a ligand for a receptor for a mouse interferon.  
     
     
         56 . The vaccine composition of  claim 1 , wherein said ligand for a cell surface polypeptide is a ligand for a receptor for a human interferon.  
     
     
         57 . The vaccine composition of  claim 54 , wherein said interferon is chosen from the group: an interferon-alpha, an interferon-beta, an interferon gamma.  
     
     
         58 . The vaccine composition of  claim 54 , wherein said ligand for a cell surface polypeptide comprises at least about 5 contiguous amino acids of an interferon.  
     
     
         59 . The vaccine composition of  claim 58 , wherein said interferon is chosen from the group: an interferon-alpha, an interferon-beta, an interferon gamma.  
     
     
         60 . The vaccine composition of  claim 1 , wherein said ligand for a cell surface polypeptide comprises an interferon.  
     
     
         61 . The vaccine composition of  claim 60  wherein said interferon is chosen from the group: an interferon-alpha, an interferon-beta, an interferon gamma.  
     
     
         62 . The vaccine composition of  claim 1 , wherein said ligand for a cell surface polypeptide is a ligand for a mouse TNF-alpha receptor.  
     
     
         63 . The vaccine composition of any of  claim 1 , wherein said ligand for a cell surface polypeptide comprises at least about five contiguous amino acids of a mouse TNF-alpha.  
     
     
         64 . The vaccine composition of  claim 1 , wherein said ligand for a cell surface polypeptide comprises a mouse TNF-alpha.  
     
     
         65 . The vaccine composition of  claim 1 , wherein said ligand for a cell surface polypeptide is a ligand for a human TNF-alpha receptor.  
     
     
         66 . The vaccine composition of  claim 1 , wherein said ligand for a cell surface polypeptide comprises at least about five contiguous amino acids of a human TNF-alpha.  
     
     
         67 . The vaccine composition of  claim 1 , wherein said ligand for a cell surface polypeptide comprises a human TNF-alpha.  
     
     
         68 . The vaccine composition of  claim 1 , wherein said ligand for a cell surface polypeptide is a ligand for a mouse flt-3 receptor.  
     
     
         69 . The vaccine composition of  claim 1 , wherein said ligand for a cell surface polypeptide comprises at least about five contiguous amino acids of a mouse flt-3.  
     
     
         70 . The vaccine composition of  claim 1 , wherein said ligand for a cell surface polypeptide comprises a mouse flt-3.  
     
     
         71 . The vaccine composition of  claim 1 , wherein said ligand for a cell surface polypeptide is a ligand for a human flt-3 receptor.  
     
     
         72 . The vaccine composition of  claim 1 , wherein said ligand for a cell surface polypeptide comprises at least about five contiguous amino acids of a human flt-3.  
     
     
         73 . The vaccine composition of  claim 1 , wherein said ligand for a cell surface polypeptide comprises a human flt-3.  
     
     
         74 . The vaccine composition of  claim 1 , wherein said fusion polypeptide further comprises a linker interposed between said first and second amino acid sequences.  
     
     
         75 . The vaccine composition of  claim 74 , wherein said linker has the formula (Gly x Ser) n , wherein n is an integer between 1 and 15, and x is an integer between 1 and 10.  
     
     
         76 . The vaccine composition of  claim 1 , which comprises said fusion polypeptide bound to a carbohydrate on said antigen bearing target.  
     
     
         77 . The vaccine composition of  claim 1 , in which at least some of said fusion polypeptide is not bound to said antigen bearing target.  
     
     
         78 . The vaccine composition of  claim 1 , wherein said antigen bearing target is a cell and said vaccine composition comprises said fusion polypeptide bound to a carbohydrate on the surface of said cell.