Antigen delivery system

Abstract

Adjuvants for administration, particularly for mucosal administration, of an antigen, are described, as well as compositions comprising the described adjuvant in combination with an antigen and a physiologicially acceptable vehicle. Methods of eliciting and enhancing an immune response utilizing the adjuvant compositions of the invention are also described.

What is claimed is:  
     
         1 . A method of eliciting an immune response to an antigen in a mammal, comprising administering to a mammalian host an effective amount of a composition comprising: 
 i) an adjuvant containing 0.01-70% v/v of glycerides selected from the group consisting of monoglycerides, diglycerides, and mixtures thereof, said glycerides having the formula (I):                          wherein R 1 , R 2 , and R 3  are independently selected from the group consisting of 
 saturated or unsaturated C 6-24  fatty acids, water soluble polymers, and mixtures thereof, provided that the glyceride contains at least one water soluble polymer;  
   ii) at least one antigen; and    iii) a physiologically acceptable aqueous vehicle.    
     
     
         2 . The method according to  claim 1 , wherein the water soluble polymers consist of PEG 2-30  residues of polyoxyethylene, or derivatives thereof, having 2-30 polyoxyethylene units.  
     
     
         3 . The method according to  claim 1 , wherein the v/v-% ratio of monoglycerides to diglycerides is from about 0.1:99.9 to about 99.9:0.1.  
     
     
         4 . The method according to  claim 1 , wherein the glycerides have a structure selected from the group consisting of:  
       
         
           
           
               
               
           
         
       
       and the mixtures of II-V.  
     
     
         5 . The method according to  claim 1 , wherein R 1 , R 2 , and R 3  are saturated C 6-14  fatty acids.  
     
     
         6 . The method according to  claim 1 , wherein the glycerides have a concentration of from about 0.1% to about 99% by weight.  
     
     
         7 . The method according to  claim 1 , wherein chiral carbons in the glyceride are either S- or R-form.  
     
     
         8 . The method according to  claim 1 , wherein the antigen is in a particulate form.  
     
     
         9 . The method according to  claim 1 , further comprising one or more components selected from the group consisting of: surfactants, absorption promoters, water absorbing polymers, substances which inhibit enzymatic degradation, alcohols, organic solvents, oils, pH-controlling agents, solubilizers, stabilizers, HLB-controlling agents, viscosity controlling agents, preservatives, osmotic pressure controlling agents, propellants, air displacement, water, and mixtures thereof.  
     
     
         10 . The method according to  claim 1 , wherein the antigen is selected from the group consisting of tetanus toxoid, hemagglutinin molecules from influenza virus, diphtheria toxoid, HIV gp120, IgA protease, insulin peptide B, Spongospora subterranea antigen, vibriose antigens, Salmonella antigens, pneumococcus antigens, respiratory syncytial virus antigens, Haemophilus influenza outer membrane proteins, Helicobacterpylori urease, Neisseria meningitidis pilins and N. gonorrhoeae pilins.  
     
     
         11 . The method according to  claim 6 , wherein the glycerides have a concentration of about 1 to about 15% by weight.  
     
     
         12 . The method according to  claim 1 , wherein (i) is a monoglyceride and diglyceride mixture of caprylic and capric acid containing 3 to 6 polyoxyethylene units.  
     
     
         13 . The method according to  claim 1 , wherein said mammal is a human.  
     
     
         14 . A method of eliciting an immune response to an antigen in a mammal, comprising administering to a mammalian host an effective amount of a composition comprising: 
 i) an adjuvant containing 0.01-70% v/v of glycerides selected from the group consisting of monoglycerides, diglycerides, and mixtures thereof, said glycerides having the formula (I):                          wherein R 1 , R 2 , and R 3  are independently selected from the group consisting of 
 saturated or unsaturated C 6-24  fatty acids, water soluble polymers, and mixtures thereof, provided that the glyceride contains at least one water soluble polymer and provided that one of the groups R 1 , R 2  and R 3  is replaced by bound antigen; and  
   ii) a physiologically acceptable aqueous vehicle.    
     
     
         15 . The method according to  claim 14 , wherein the antigen is in a dissolved form.  
     
     
         16 . A method of eliciting an immune response to an antigen in a mammal, comprising administering to a mammalian host an effective amount of a composition comprising: 
 i) an adjuvant containing 0.01-70% v/v of a monoglyceride and diglyceride mixture of caprylic and capric acid containing polyoxyethylene units;    ii) at least one antigen of a pathogenic microorganism; and    iii) a physiologically acceptable aqueous vehicle.    
     
     
         17 . A method according to  claim 16 , wherein the adjuvant contains three to six polyoxyethylene units.  
     
     
         18 . A method of eliciting an immune response to an antigen in a mammal, comprising administering to a mammalian host an effective amount of a composition comprising: 
 i) an adjuvant containing 0.01-70% v/v of glycerides selected from the group consisting of monoglycerides, diglycerides, and mixtures thereof, said glycerides having the formula (I):                          wherein R 1 , R 2 , and R 3  are independently selected from the group consisting of saturated or unsaturated C 6-24  fatty acids, water soluble polymers, and mixtures thereof, provided that the glyceride contains at least one water soluble polymer;    ii) at least one antigen of a pathogenic microorganism; and    iii) a physiologically acceptable aqueous vehicle.    
     
     
         19 . A method of eliciting an immune response to an antigen in a mammal, comprising administering to a mammalian host an effective amount of a composition comprising: 
 i) an adjuvant containing 0.01-70% v/v of glycerides selected from the group consisting of monoglycerides, diglycerides, and mixtures thereof, wherein the v/v% ratio of monoglycerides to diglycerides is from about 5:95 to about 95:5, said glycerides having the formula (I):                          wherein R 1 , R 2 , and R 3  are independently selected from the group consisting of saturated or unsaturated C 6-24  fatty acids, water soluble polymers, and mixtures thereof, provided that the glyceride contains at least one water soluble polymer;    ii) at least one antigen; and    iii) a physiologically acceptable aqueous vehicle.    
     
     
         20 . A method of delivering an antigen to a mucosal surface of a mammal, comprising administering to a mammalian host an effective amount of a composition comprising: 
 i) an adjuvant containing 0.01-70% v/v of glycerides selected from the group consisting of monoglycerides, diglycerides, and mixtures thereof, said glycerides having the formula (I):                          wherein R 1 , R 2 , and R 3  are independently selected from the group consisting of saturated or unsaturated C 6-24  fatty acids, water soluble polymers, and mixtures thereof, provided that the glyceride contains at least one water soluble polymer;    ii) at least one antigen; and    iii) a physiologically acceptable aqueous vehicle.    
     
     
         21 . A method of delivering an antigen to a mucosal surface of a mammal, comprising administering to a mammalian host an effective amount of a composition comprising: 
 i) an adjuvant containing 0.01-70% v/v of glycerides selected from the group consisting of monoglycerides, diglycerides, and mixtures thereof, said glycerides having the formula (I):                          wherein R 1 , R 2 , and R 3  are independently selected from the group consisting of 
 saturated or unsaturated C 6-24  fatty acids, water soluble polymers, and mixtures thereof, provided that the glyceride contains at least one water soluble polymer and provided that one of the groups R 1 , R 2  and R 3  is replaced by bound antigen; and  
   ii) a physiologically acceptable aqueous vehicle.    
     
     
         22 . The method according to  claim 21  wherein said mucosal surface is a mucosal surface of the nose, lungs, mouth, eye, ear, gastrointestinal tract, genital tract, vagina or rectum.  
     
     
         23 . The method according to  claim 22  wherein said mucosa surface is that of the nose.