Intradermal delivery of vaccines and gene therapeutic agents via microcannula

Abstract

Methods and devices for administration of vaccines and gene therapeutic agents into the intradermal layer of skin.

What is claimed is:  
     
         1 . A method for delivering a vaccine to a mammal, said method comprising intradermally administering the vaccine through at least one hollow needle having an outlet with an exposed height between 0 and 1 mm , said outlet being inserted into the skin to a depth of between 0.5 mm and 2 mm.  
     
     
         2 . The method of  claim 1  wherein the vaccine is administered with a device comprising 
 a hub portion being attachable to a prefillable reservoir storing the vaccine;  
 at least one hollow microneedle supported by said hub portion and having a forward tip extending away from said hub portion; and  
 a limiter portion surrounding said microneedle(s) and extending away from said hub portion toward said forward tip of said microneedle(s), said limiter including a generally flat skin engaging surface extending in a plane generally perpendicular to an axis of said microneedle(s) and adapted to be received against the skin of a mammal to administer an intradermal injection of the vaccine, said microneedle(s) forward tip(s) extending beyond said skin engaging surface a distance approximately 0.5 mm to 2.0 mm wherein said limiter portion limits penetration of the microneedle(s) into the dermal layer of skin of the mammal.  
 
     
     
         3 . The method of  claim 1  wherein delivery of the vaccine occurs at a depth between 0.025 mm and 2.5 mm in the skin of the mammal.  
     
     
         4 . The method of  claim 1  wherein the delivered vaccine induces an immune response in the mammal that is equal to or greater than the response after delivery of the same amount of vaccine by subcutaneous or intramuscular injection.  
     
     
         5 . The method of  claim 1  wherein the delivered vaccine induces an immune response in the mammal that is equal to or greater than the response after delivery of a greater amount of vaccine by subcutaneous or intramuscular injection.  
     
     
         6 . The method of  claim 1  wherein the needle is a microneedle between about 31 to 50 gauge.  
     
     
         7 . The method of  claim 1  wherein the needle has a bevel angle between 20° and 90°.  
     
     
         8 . The method of  claim 7  wherein the needle has a bevel angle between 25° and 40°.  
     
     
         9 . The method of  claim 6  wherein the length of the needle inserted into the skin is to a depth from about 0.5 mm to about 1.7 mm.  
     
     
         10 . The method of  claim 6  wherein the microneedle is in an array of microneedles.  
     
     
         11 . The method of  claim 1  wherein the vaccine comprises a live attenuated virus.  
     
     
         12 . The method of  claim 1  wherein the vaccine comprises a live attenuated bacterium.  
     
     
         13 . The method of  claim 1  wherein the vaccine comprises an inactivated or killed virus.  
     
     
         14 . The method of  claim 13  wherein the vaccine additionally comprises an adjuvant.  
     
     
         15 . The method of  claim 13  wherein the vaccine is an influenza vaccine.  
     
     
         16 . The method of  claim 1  wherein the vaccine comprises an inactivated or killed bacterium.  
     
     
         17 . The method of  claim 1  wherein the vaccine comprises a nucleic acid.  
     
     
         18 . The method of  claim 17  wherein a peptide or protein encoded by the nucleic acid is expressed in the mammal.  
     
     
         19 . The method of  claim 17  wherein the vaccine additionally comprises an adjuvant.  
     
     
         20 . The method of  claim 17  wherein the vaccine is an influenza vaccine.  
     
     
         21 . The method of  claim 1  wherein the vaccine comprises a live nonattenuated bacterium or virus.  
     
     
         22 . The method of  claim 1  wherein the vaccine comprises mammalian cells or components thereof.  
     
     
         23 . The method of  claim 1  wherein the vaccine comprises a polysaccharide or polysaccharide conjugate.  
     
     
         24 . The method of  claim 1  wherein the vaccine comprises a protein or peptide.  
     
     
         25 . The method of  claim 1  wherein the needle(s) are inserted substantially perpendicularly to the skin.  
     
     
         26 . The method of  claim 1  that additionally comprises administering a second vaccine intramuscularly, subcutaneously, mucosally, intraperitoneally, intravenously, topically or epidermally.  
     
     
         27 . The method of  claim 26  wherein the second vaccine is the same composition as said vaccine.  
     
     
         28 . The method of  claim 26  wherein the second vaccine is a different composition than said vaccine.  
     
     
         29 . The method of  claim 26  wherein the second vaccine is a different vaccine class from said vaccine.  
     
     
         30 . The method of  claim 26  wherein said second vaccine is administered simultaneously with said vaccine.  
     
     
         31 . The method of  claim 26  wherein said second vaccine is administered subsequently to said vaccine.  
     
     
         32 . The method of  claim 1  that additionally comprises administering a second vaccine through at least one hollow needle having an outlet with an exposed height between 0 and 1 mm , said outlet being inserted into the skin to a depth of between 0.5 mm and 2 mm.  
     
     
         33 . The method of  claim 32  wherein delivery of the second vaccine occurs at a depth between 0.025 mm and 2.5 mm in the skin of the mammal.  
     
     
         34 . The method of  claim 32  wherein the second vaccine is administered simultaneously with said vaccine.  
     
     
         35 . The method of  claim 32  wherein the second vaccine is administered subsequent to said vaccine.  
     
     
         36 . The method of  claim 35  wherein the second vaccine is administered one day to six weeks after said vaccine.  
     
     
         37 . The method of  claim 32  wherein the second vaccine is a different vaccine class than said vaccine.  
     
     
         38 . The method of  claim 32  wherein the second vaccine is the same composition than said vaccine.  
     
     
         39 . The method of  claim 32  wherein the second vaccine is a different composition than said vaccine.  
     
     
         40 . A method for delivering a vaccine to a mammal, said method comprising: 
 a) contacting the skin of the mammal with a device having a dermal-access means for accurately targeting a dermal space of the skin at a depth between 0.025 mm and 2.5 mm with the vaccine; and    b) delivering the vaccine to the dermal space.    
     
     
         41 . The method of  claim 40  wherein the delivered vaccine induces an immune response in the mammal that is equal to or greater than the response after delivery of the same amount of vaccine by subcutaneous or intramuscular injection.  
     
     
         42 . The method of  claim 40  wherein the delivered vaccine induces an immune response in the mammal that is equal to or greater than the response after delivery of a greater amount of vaccine by subcutaneous or intramuscular injection.  
     
     
         43 . A method for delivering a gene therapeutic agent to a mammal, said method comprising administering the therapeutic agent through at least one small gauge hollow needle having an outlet with an exposed height between 0 and 1 mm, said outlet being inserted into the skin to a depth of between 0.5 mm and 2 mm.  
     
     
         44 . The method of  claim 43 , wherein delivery of the therapeutic agent occurs at a depth between 0.025 mm and 2.5 mm in the skin of the mammal.  
     
     
         45 . The method of  claim 43  wherein a peptide or protein encoded by the gene therapeutic agent is expressed in the mammal.  
     
     
         46 . The method of  claim 45  wherein expression occurs in skin cells of the mammal.  
     
     
         47 . The method of  claim 43  wherein the needle is a microneedle between 31 to 50 gauge.  
     
     
         48 . The method of  claim 43  wherein the needle has a bevel angle between 20° and 90°.  
     
     
         49 . The method of  claim 48  wherein the needle has a bevel angle between 25° and 40°.  
     
     
         50 . The method of  claim 43  wherein the needle has a length from about 0.5 mm to about 1.7 mm.  
     
     
         51 . The method of  claim 47  wherein the microneedle is contained in an array of microneedles.  
     
     
         52 . The method of  claim 43  wherein the gene therapeutic agent comprises a nucleic acid.  
     
     
         53 . The method of  claim 43  wherein the needle(s) are inserted substantially perpendicularly to the skin.  
     
     
         54 . A kit comprising a delivery device having at least one hollow microneedle designed to intradermally deliver a substance to a depth between 0.025 and 2.5 mm, said delivery device being adapted to receive a reservoir that contains a gene therapeutic agent or vaccine such that the microneedle is in communication therewith.  
     
     
         55 . The kit of  claim 54  that additionally comprises an effective dosage of a vaccine or gene therapeutic.  
     
     
         56 . The kit of  claim 55  wherein the dosage is contained in a reservoir that is an integral part of, or is capable of being functionally attached to, the delivery device.  
     
     
         57 . The kit of  claim 54  wherein the hollow microneedle is between about 31 to 50 gauge.  
     
     
         58 . The kit of  claim 54  wherein the device comprises an array of microneedles.  
     
     
         59 . The kit of  claim 54  wherein the device comprises 
 a hub portion being attachable to a prefillable reservoir storing the vaccine;  
 at least one microneedle supported by said hub portion and having a forward tip extending away from said hub portion; and  
 a limiter portion surrounding said microneedle and extending away from said hub portion toward said forward tip of said microneedle, said limiter including a generally flat skin engaging surface extending in a plane generally perpendicular to an axis of said microneedle and adapted to be received against the skin of a mammal to administer an intradermal injection of the vaccine, said microneedle forward tip extending beyond said skin engaging surface a distance approximately 0.5 mm to 2.0 mm wherein said limiter portion limits penetration of the microneedle into the dermal layer of skin of the mammal.  
 
     
     
         60 . A kit comprising a dermal access means designed to intradermally deliver a substance to a depth between 0.025 and 2.5 mm, said dermal access means being adapted to receive a reservoir that contains a gene therapeutic agent or vaccine such that the dermal access means is in communication therewith.