Use of hyaluronic acid polymers for mucosal delivery of vaccine and adjuvants

Abstract

Compositions are provided which include hyaluronic acid derivatives in combination with vaccine antigens, and optionally adjuvants, for mucosal delivery. Also provided are methods of making the compositions, as well as methods of immunization using the same.

1 . A composition comprising an hyaluronic acid ester polymer in the form of a microsphere, a detoxified mutant of a bacterial ADP-ribosylating toxin, and a selected antigen, wherein said antigen is present in an amount of approximately 0.1% to about 40% (w/w) antigen to hyaluronic acid polymer.  
   
   
       2 . The composition of  claim 1 , wherein said antigen is present in an amount of approximately 2% to about 25% (w/w) antigen to hyaluronic acid polymer.  
   
   
       3 . The composition of  claim 1 , wherein the hyaluronic acid ester is selected from the group consisting of an hyaluronic acid where from about 75% to about 100% of free carboxyl groups are esterified with one or more alkyl groups, and a crosslinked derivative of hyaluronic acid in which about 0.5% to about 20% of the carboxyl groups of the hyaluronic acid polymer are crosslinked to hydroxyl groups of the same or a different hyaluronic acid molecule.  
   
   
       4 . (canceled)  
   
   
       5 . The composition of  claim 1 , wherein the adjuvant is a detoxified mutant of a bacterial ADP-ribosylating toxin is selected from the group consisting of LT-K63 and LT-R72.  
   
   
       6 . The composition of  claim 1 , wherein the selected antigen is a viral antigen.  
   
   
       7 . The composition of  claim 6 , wherein the selected antigen is an influenza antigen.  
   
   
       8 . (canceled)  
   
   
       9 . The composition of  claim 1 , wherein the selected antigen is entrapped in the microsphere.  
   
   
       10 . The composition of  claim 1 , wherein the selected antigen is adsorbed to the microsphere.  
   
   
       11 . A composition comprising (a) a microsphere comprised of an hyaluronic acid ester polymer selected from the group consisting of an hyaluronic acid where from about 75% to about 100% of free carboxyl groups are esterified with one or more alkyl groups, and a crosslinked derivative of hyaluronic acid in which about 0.5% to about 20% of the carboxyl groups of the hyaluronic acid polymer are crosslinked to hydroxyl groups of the same or a different hyaluronic acid molecule; (b) a selected antigen entrapped in, or adsorbed to, the microsphere, wherein said antigen is present in an amount of approximately 2% to about 25% (w/w) antigen to hyaluronic acid polymer; and (c) an immunological adjuvant.  
   
   
       12 . The composition of  claim 11 , wherein the selected antigen is entrapped in the microsphere.  
   
   
       13 . (canceled)  
   
   
       14 . A method of making a pharmaceutical composition which comprises combining the composition of  claim 1  with a pharmaceutically acceptable mucosal excipient.  
   
   
       15 . A method of making a pharmaceutical composition which comprises combining the composition of  claim 11  with a pharmaceutically acceptable mucosal excipient.  
   
   
       16 . A method of immunization which comprises mucosally administering a therapeutically effective amount of the pharmaceutical composition of  claim 14  to a vertebrate subject.  
   
   
       17 . A method of immunization which comprises mucosally administering a therapeutically effective amount of the pharmaceutical composition of  claim 15  to a vertebrate subject.  
   
   
       18 . The method of  claim 16  wherein the administering is done intranasally.  
   
   
       19 . The method of  claim 17  wherein the administering is done intranasally.  
   
   
       20 . (canceled)  
   
   
       21 . The composition of  claim 1 , wherein the microsphere is a nanosphere.  
   
   
       22 . The composition of  claim 11 , wherein the microsphere is a nanosphere.