Novel mucosal adjuvants and delivery systems

Abstract

Adjuvants comprising chitosan cross-linked with an aldehyde or mannosylated chitosan are provided herein. Methods of making the adjuvants and methods of combining or linking the adjuvants with antigens are also provided. The adjuvant-antigen combinations can be used in vaccine formulations and the vaccine formulations can be used in methods to vaccinate animals against the source of the antigen or to enhance the immune response in a subject.

1 . An adjuvant composition comprising a carbohydrate linked to chitosan to form a Schiff base, and wherein the carbohydrate is mannose. 
     
     
         2 . (canceled) 
     
     
         3 . (canceled) 
     
     
         4 . The composition of  claim 1 , wherein the Schiff base is not reduced. 
     
     
         5 . The composition of  claims 1 , wherein the Schiff base is reduced. 
     
     
         6 . An adjuvant composition comprising between 0.5% and 2% of an aldehyde cross-linked chitosan and Tris-HCl to quench free aldehydes. 
     
     
         7 . The composition of  claim 6 , wherein the chitosan is cross-linked with formaldehyde. 
     
     
         8 . (canceled) 
     
     
         9 . The composition of  claim 1 , further comprising an enhancing molecule, wherein the enhancing molecule is selected from the group consisting of saponin, toll-like receptors, the B subunit of a bacterial toxin, bacterial toxins, CpG motifs, liposomes, monophosphoryl lipid A, tetanus toxoid, cholera toxin B subunit, heat labile enterotoxin B subunit, and tripolyphosphate. 
     
     
         10 . (canceled) 
     
     
         11 . (canceled) 
     
     
         12 . A vaccine formulation comprising the adjuvant composition of  claims 1  and an antigen, wherein the antigen comprises a microbe. 
     
     
         13 . (canceled) 
     
     
         14 . (canceled) 
     
     
         15 . (canceled) 
     
     
         16 . The vaccine of  claim 12 , wherein the microbe is  Salmonella, Escherichia, Shigella, Bordetella, Clostridium, Mycoplasma, Staphylococcus, Streptococcus, Bacillus, Influenza,  or  Eimeria.    
     
     
         17 . The vaccine of  claim 12 , wherein the microbe is inactivated or killed. 
     
     
         18 . The vaccine of  claim 17 , wherein the microbe Is killed using formaldehyde, glutaraldehyde or formalin. 
     
     
         19 . A method of making the composition of  claim 6 , comprising dissolving chitosan in a solution of acetic acid, adding an antigen to the dissolved chitosan, combining the dissolved chitosan and antigen with an aldehyde such that the final concentration of the aldehyde is between 0.02% and 0.5% and adding Tris-HCl to quench free aldehydes. 
     
     
         20 . The method of  claim 19 , wherein the antigen is a protein or a microbial vaccine. 
     
     
         21 . (canceled) 
     
     
         22 . (canceled) 
     
     
         23 . The method of  claim 19 , wherein the aldehyde is added at a final concentration of 0.2%. 
     
     
         24 . A method of enhancing the immune response of a subject to an antigen comprising administering the vaccine formulation of  claim 12  to the subject. 
     
     
         25 . The method of  claim 24 , wherein the immune response includes an enhanced antibody response as compared to administering a vaccine without an adjuvant. 
     
     
         26 . The method of  claim 25 , wherein the enhanced antibody response is an enhanced secretory IgA antibody response as compared to administering a vaccine without an adjuvant. 
     
     
         27 . (canceled) 
     
     
         28 . The method of  claim 24 , wherein the subject is a mammal or poultry. 
     
     
         29 . The method of  claim 24 , wherein the route of administration is subcutaneous or oral. 
     
     
         30 . The method of  claim 24 , wherein the vaccine formulation Is administered in food or drinking water. 
     
     
         31 . A method of enhancing the immune response of a subject to an antigen comprising administering a vaccine formulation comprising the antigen and an adjuvant composition comprising between 0.5% and 2% of an aldehyde cross-linked chitosan in which the free aldehydes are quenched with Tris-HCl to the subject in an amount effective to enhance the immune response to the antigen.