Method for removal of viruses from blood by lectin affinity hemodialysis

Abstract

The present invention relates to a method for using lectins that bind to pathogens having high mannose surface glycoproteins or fragments thereof which contain high mannose glycoproteins, to remove them from infected blood or plasma in an extracorporeal setting. Accordingly, the present invention provides a method for reducing viral load in an individual comprising the steps of obtaining blood or plasma from the individual, passing the blood or plasma through a porous hollow fiber membrane wherein lectin molecules are immobilized within the porous exterior portion of the membrane, collecting pass-through blood or plasma and reinfusing the pass-through blood or plasma into the individual.

1 . A method of using lectin to reduce the amount of viral particles or fragments thereof in blood or plasma contaminated with a viral particles or fragments thereof, comprising: 
 providing a lectin affinity device comprising a processing chamber having lectin disposed within said processing chamber, wherein said lectin binds viral particles or fragments thereof and traps them in said processing chamber;    transferring blood or plasma contaminated with viral particles or fragments thereof into said chamber such that said viral particles or fragments thereof contact said lectin and are bound thereto; and    removing said blood or plasma from said chamber, wherein said removed blood or plasma has a reduced amount of viral particles or fragments thereof.    
     
     
         2 . The method of  claim 1 , wherein plasma contaminated with viral particles or fragments thereof is transferred into said chamber.  
     
     
         3 . The method of  claim 1 , wherein blood contaminated with viral particles or fragments thereof is transferred into said chamber.  
     
     
         4 . The method of  claim 1 , wherein said lectin is attached to a substrate.  
     
     
         5 . The method of  claim 4 , wherein said substrate is selected from the group consisting of agarose, glass beads, aminocelite, and a resin.  
     
     
         6 . The method of  claim 4 , wherein said lectin is linked to the substrate by a linker.  
     
     
         7 . The method of  claim 6 , wherein said linker is selected from the group consisting of avidin, strepavidin, biotin, protein A, and protein G.  
     
     
         8 . The method of  claim 1 , wherein said lectin is selected from the group consisting of  Galanthus nivalis  agglutinin (GNA),  Narcissus pseudonarcissus  agglutinin (NPA), cyanovirin, Conconavalin A and mixtures thereof.  
     
     
         9 . The method of  claim 1 , wherein the lectin is GNA.  
     
     
         10 . The method of  claim 1 , wherein said lectin binds to a viral coat protein or a fragment thereof.  
     
     
         11 . The method of  claim 1 , wherein the virus is an envelope virus.  
     
     
         12 . The method of  claim 1 , wherein the virus is HIV.  
     
     
         13 . The method of  claim 1 , wherein the virus is HCV.  
     
     
         14 . The method of  claim 13  wherein said processing chamber further comprises a porous membrane, said membrane configured such that said viral particles or fragments thereof pass through said membrane and contact said lectin; and wherein blood cells are prevented from passing through said membrane and contacting said lectin.  
     
     
         15 . The method of  claim 14 , wherein said membrane has pores about 200-500 nm in diameter.  
     
     
         16 . The method of  claim 14 , wherein said membrane is a porous hollow fiber membrane.  
     
     
         17 . The method of  claim 14 , wherein said lectin is attached to a substrate.  
     
     
         18 . The method of  claim 17 , wherein said substrate is selected from the group consisting of agarose, glass beads, aminocelite, and a resin.  
     
     
         19 . The method of  claim 17 , wherein lectin is linked to said substrate by a linker.  
     
     
         20 . The method of  claim 19 , wherein said linker is selected from the group consisting of avidin, strepavidin, biotin, protein A, and protein G.  
     
     
         21 . The method of  claim 14 , wherein said lectin is selected from the group consisting of  Galanthus nivalis  agglutinin (GNA),  Narcissus pseudonarcissus  agglutinin (NPA), cyanovirin, Conconavalin A and mixtures thereof.  
     
     
         22 . The method of  claim 14 , wherein the lectin is GNA.  
     
     
         23 . The method of  claim 14 , wherein said lectin binds to a viral coat protein or a fragment thereof.  
     
     
         24 . The method of  claim 14 , wherein the virus is an envelope virus.  
     
     
         25 . The method of  claim 14 , wherein the virus is HIV.  
     
     
         26 . The method of  claim 14 , wherein the virus is HCV.  
     
     
         27 . A method of using lectin to reduce the amount of viral particles or fragments thereof in blood or plasma contaminated with viral particles or fragments thereof, comprising: 
 passing blood or plasma contaminated with viral particles or fragments thereof through at least one porous hollow fiber membrane contained in a cartridges wherein lectin is disposed within an extrachannel space of said cartridge proximate to an exterior surface of said at least one membrane, and wherein the lectin binds viral particles or fragments thereof and traps them in said extrachannel space; and    collecting pass-through blood or plasma, wherein said pass-through blood or plasma has a reduced amount of viral particles or fragments thereof.    
     
     
         28 . The method of  claim 27 , further comprising repeating said passing and collecting steps with said pass-through blood or plasma to further reduce the amount of said viral particles or fragments thereof in said pass-through blood or plasma.  
     
     
         29 . The method of  claim 27 , wherein said at least one porous membrane has a pore size to allow passage of intact viral particles or fragments thereof through said pores and wherein said pore size excludes blood cells from passing through said pores.  
     
     
         30 . The method of  claim 27 , wherein said membranes have pores about 200-500 nm in diameter.  
     
     
         31 . The method of  claim 27 , wherein said membranes have an inside diameter of about 0.3 mm and an outside diameter of about 0.5 mm.  
     
     
         32 . The method of  claim 27 , wherein said lectin is attached to a substrate.  
     
     
         33 . The method of  claim 32 , wherein said substrate is selected from the group consisting of agarose, glass beads, aminocelite, and a resin.  
     
     
         34 . The method of  claim 32 , wherein lectin is linked to said substrate by a linker.  
     
     
         35 . The method of  claim 34 , wherein said linker is selected from the group consisting of avidin, strepavidin, biotin, protein A, and protein G.  
     
     
         36 . The method of  claim 27 , wherein the lectin is selected from the group consisting of  Galanthus nivalis  agglutinin (GNA),  Narcissus pseudonarcissus  agglutinin (NPA), cyanovirin, Conconavalin A and mixtures thereof.  
     
     
         37 . The method of  claim 36 , wherein the lectin is GNA.  
     
     
         38 . The method of  claim 27 , wherein the lectin binds to a viral coat protein or a fragment thereof.  
     
     
         39 . The method of  claim 27 , wherein the virus is an envelope virus.  
     
     
         40 . The method of  claim 27 , wherein the virus is HIV.  
     
     
         41 . The method of  claim 27 , wherein the virus is HCV.  
     
     
         42 . A lectin affinity device for removing viral particles or fragments thereof from contaminated blood or plasma comprising: 
 a processing chamber configured to receive blood or plasma contaminated with viral particles or fragments thereof;    lectin disposed within said processing chamber; and    a porous membrane, said membrane configured such that when blood or plasma contaminated with viral particles or fragments thereof is disposed in said processing chamber, viral particles or fragments thereof pass through said membrane and contact said lectin and are bound thereto, and wherein blood cells are prevented from passing through said membrane and contacting said lectin.    
     
     
         43 . The lectin affinity device of  claim 42 , wherein said membrane has pores about 200-500 nm in diameter.  
     
     
         44 . The lectin affinity device of  claim 42 , wherein said lectin is attached to a substrate.  
     
     
         45 . The lectin affinity device of  claim 44 , wherein said substrate is selected from the group consisting of agarose, glass beads, aminocelite, and a resin.  
     
     
         46 . The lectin affinity device of  claim 44 , wherein lectin is linked to said substrate by a linker.  
     
     
         47 . The lectin affinity device of  claim 46 , wherein said linker is selected from the group consisting of avidin, strepavidin, biotin, protein A, and protein G.  
     
     
         48 . The lectin affinity device of  claim 42 , wherein said lectin is selected from the group consisting of  Galanthus nivalis  agglutinin (GNA),  Narcissus pseudonarcissus  agglutinin (NPA), cyanovirin, Conconavalin A and mixtures thereof.  
     
     
         49 . The lectin affinity device of  claim 48 , wherein the lectin is GNA.  
     
     
         50 . The lectin affinity device of  claim 42 , wherein the lectin binds to a viral coat protein or a fragment thereof.  
     
     
         51 . The lectin affinity device of  claim 42 , wherein the virus is an envelope virus.  
     
     
         52 . The lectin affinity device of  claim 42 , wherein the virus is HIV.  
     
     
         53 . The lectin affinity device of  claim 42 , wherein the virus is HCV.  
     
     
         54 . The lectin affinity device of  claim 42 , wherein said processing chamber further comprises an inlet port and an outlet port; 
 said porous membrane is one or more porous hollow fiber membranes wherein a channel of said hollow fiber membranes is in fluidic communication with said inlet and said outlet ports;    said device having an extrachannel space within said chamber which surrounds said hollow fiber membranes; and    said lectin is disposed within said extrachannel space proximate to an exterior surface of said membranes, wherein said lectin binds viral particles or fragments thereof and traps them in the extrachannel space.    
     
     
         55 . The lectin affinity device of  claim 54 , wherein said membranes have pores about 200-500 nm in diameter.  
     
     
         56 . The lectin affinity device of  claim 54 , wherein said membranes have an inside diameter of about 0.3 mm and an outside diameter of about 0.5 mm.  
     
     
         57 . The lectin affinity device of  claim 54 , further comprising an access port in said processing chamber configured to access said extrachannel space.  
     
     
         58 . The lectin affinity device of  claim 54 , further comprising an exterior chamber surrounding said processing chamber, said exterior chamber having an inlet and an outlet port configured to allow circulation of a fluid into said exterior chamber.  
     
     
         59 . The lectin affinity device of  claim 54 , wherein said lectin is attached to a substrate.  
     
     
         60 . The lectin affinity device of  claim 59 , wherein said substrate is selected from the group consisting of agarose, glass beads, aminocelite, and a resin.  
     
     
         61 . The lectin affinity device of  claim 59 , wherein lectin is linked to said substrate by a linker.  
     
     
         62 . The lectin affinity device of  claim 61 , wherein said linker is selected from the group consisting of avidin, strepavidin, biotin, protein A, and protein G.  
     
     
         63 . The lectin affinity device of  claim 54 , wherein said lectin is selected from the group consisting of  Galanthus nivalis  agglutinin (GNA),  Narcissus pseudonarcissus  agglutinin (NPA), cyanovirin, Conconavalin A and mixtures thereof.  
     
     
         64 . The lectin affinity device of  claim 63 , wherein the lectin is GNA.  
     
     
         65 . The lectin affinity device of  claim 54 , wherein the lectin binds to a viral coat protein or a fragment thereof.  
     
     
         66 . The lectin affinity device of  claim 54 , wherein the virus is an envelope virus.  
     
     
         67 . The lectin affinity device of  claim 54 , wherein the virus is HIV.  
     
     
         68 . The lectin affinity device of  claim 54 , wherein the virus is HCV.