Delivery system to modulate immune response

Abstract

A microsphere containing an immunogen bound to an inert particle having a mesh size of greater than about 35 mesh for site-specific release and induction of an immune response. The immune response may be an overall enhanced T lymphocyte immune response or a selective response. The physical and chemical characteristics and/or modes of administration of the microsphere may be engineered to increase T H 1 lymphocytes for treatment of cancer or infectious disease. The microencapsulated immunogen has an enteric coating for oral administration.

What is claimed is:  
     
         1 . A method of inducing an immune response in a mammal comprising administering a microsphere comprising an immunogen bound to an inert particle to a small intestine of said mammal, said inert particle having a mesh size greater than about 35 mesh.  
     
     
         2 . The method of  claim 1  wherein said microsphere is administered orally and said microsphere comprises an enteric coated microsphere.  
     
     
         3 . The method of  claim 1  wherein said microsphere is administered in a gel capsule.  
     
     
         4 . The method of  claim 1  wherein said immunogen is selected from the group consisting of a peptide, a protein fragment, a protein, a gene, a gene fragment, a DNA, an RNA and combinations thereof.  
     
     
         5 . The method of  claim 1  wherein said immunogen is a vaccine.  
     
     
         6 . The method of  claim 1  further comprising administering a potentiating agent bound to an inert particle, said inert particle selected from the group consisting of an immunogen-bound inert particle and a non-immunogen bound inert particle.  
     
     
         7 . The method of  claim 1  wherein a plurality of microspheres are administered to selectively induce the immune response.  
     
     
         8 . The method of  claim 7  wherein said microspheres have compositions selected from the group consisting of different inert particle sizes, different inert particle compositions, different enteric coatings, different formulations and combinations thereof.  
     
     
         9 . The method of  claim 1  wherein said microsphere containing said immunogen induces an increase in the number of T lymphocytes.  
     
     
         10 . The method of  claim 9  wherein said microsphere containing said immunogen induces an increase in a cell population selected from the group consisting of a T H 1 lymphocyte, a cytotoxic T lymphocyte (CTL), and combinations thereof.  
     
     
         11 . The method of  claim 1  wherein said inert particle has a mesh size greater than about 40 mesh.  
     
     
         12 . The method of  claim 1  where said immunogen is contained on an inert particle selected from the group consisting of a nonpareil, a silica powder, a salt crystal and a sugar crystal.  
     
     
         13 . A method of treating cancer in a mammal comprising administering a microsphere comprising an immunogen bound to an inert particle to a small intestine of said mammal, said inert particle having a mesh size greater than about 35 mesh.  
     
     
         14 . The method of  claim 13  wherein said microsphere is administered orally and said microsphere comprises an enteric coated microsphere.  
     
     
         15 . The method of  claim 13  wherein said microsphere is administered in a gel capsule.  
     
     
         16 . The method of  claim 13  wherein said immunogen is selected from the group consisting of a peptide, a protein fragment, a protein, a gene, a gene fragment, a DNA, an RNA and combinations thereof.  
     
     
         17 . The method of  claim 13  wherein said immunogen is a vaccine.  
     
     
         18 . The method of  claim 13  further comprising administering a potentiating agent bound to an inert particle, said inert particle selected from the group consisting of an immunogen-bound inert particle and a non-immunogen bound inert particle.  
     
     
         19 . The method of  claim 13  wherein a plurality of microspheres are administered to selectively induce the immune response.  
     
     
         20 . The method of  claim 19  wherein said microspheres have compositions selected from the group consisting of different inert particle sizes, different inert particle compositions, different enteric coatings, different formulations and combinations thereof.  
     
     
         21 . The method of  claim 13  wherein said microsphere containing said immunogen induces an increase in the number of T lymphocytes.  
     
     
         22 . The method of  claim 21  wherein said microsphere containing said immunogen induces an increase in a cell population selected from the group consisting of a T H 1 lymphocyte, a cytotoxic T lymphocyte (CTL), and combinations thereof.  
     
     
         23 . The method of  claim 13  wherein said inert particle has a mesh size greater than about 40 mesh.  
     
     
         24 . The method of  claim 13  wherein said immunogen is contained on an inert particle selected from the group consisting of a nonpareil, a silica powder, a salt crystal and a sugar crystal.  
     
     
         25 . A method of inducing an immune response in a mammal comprising orally administering to said mammal a microsphere comprising an enteric-coated inert particle containing a protein immunogen, said particle having a mesh size greater than about 40 mesh.  
     
     
         26 . The method of  claim 25  further comprising administering a potentiating agent bound to an inert particle, said inert particle selected from the group consisting of an immunogen-bound inert particle and a non-immunogen bound inert particle.  
     
     
         27 . The method of  claim 25  wherein a plurality of microspheres are administered to selectively induce the immune response.  
     
     
         28 . The method of  claim 27  wherein said microspheres have compositions selected from the group consisting of different inert particle sizes, different inert particle compositions, different enteric coatings, different formulations and combinations thereof.  
     
     
         29 . The method of  claim 25  wherein the immune response comprises an increase in a T lymphocyte population.  
     
     
         30 . The method of  claim 29  wherein the immune response comprises an increase in a cell population selected from the group consisting of a T H 1 lymphocyte, a cytotoxic T lymphocyte (CTL), and combinations thereof.  
     
     
         31 . A composition adapted to induce an immune response comprising an immunogen contained on an inert particle and having an enteric coating, said inert particle having a mesh size greater than about 35 mesh.  
     
     
         32 . The composition of  claim 31  contained in a gel capsule.  
     
     
         33 . The composition of  claim 31  further comprising a potentiating agent.