Zwitterionic immunomodulators for the treatment of asthma and allergy

Abstract

Methods and products for treating and protecting against asthma and allergic conditions are provided. The methods and products are related to certain naturally occurring and synthetic zwitterionic polymers which are found to induce certain T regulatory (Treg) cells and to exert immunosuppressive effects in vitro and in vivo.

We claim:  
     
         1 . A method for treating an allergic condition other than asthma in a subject, comprising: 
 administering to a subject having an allergic condition other than asthma an isolated polymer in an effective amount to treat the allergic condition, wherein the polymer comprises repeating units of a charge motif characteristic of  B. fragilis  polysaccharide A (PSA), the motif being a positively charged free amino moiety and a negatively charged moiety selected from the group consisting of carboxyl, phosphate, phosphonate, sulfate, and sulfonate.    
     
     
         2 . The method of  claim 1 , wherein the motif is a positively charged free amino moiety and a negatively charged moiety selected from the group consisting of phosphate, phosphonate, sulfate, and sulfonate.  
     
     
         3 . The method of  claim 1 , wherein the administering comprises delivering an aerosol of the polymer to an airway of the subject.  
     
     
         4 . The method of  claim 1 , wherein the subject is free of symptoms otherwise calling for treatment with the polymer.  
     
     
         5 . The method of  claim 1 , wherein the polymer is a polysaccharide.  
     
     
         6 . The method of  claim 1 , wherein the polymer is a bacterial capsular polysaccharide.  
     
     
         7 . The method of  claim 1 , wherein the polymer is PSA1.  
     
     
         8 . The method of  claim 1 , wherein the polymer is PSA2.  
     
     
         9 . The method of  claim 1 , wherein the polymer is PSB.  
     
     
         10 . The method of  claim 1 , wherein the polymer is  Streptococcus pneumoniae  capsular polysaccharide 1 (CP1).  
     
     
         11 . The method of  claim 1 , wherein the polymer is de-N-acetylated  Salmonella typhi  Vi antigen.  
     
     
         12 . The method of  claim 1 , wherein the polymer is aminated pectin.  
     
     
         13 . The method of  claim 1 , wherein the polymer is synthetic peptidoglycan Compound 15.  
     
     
         14 . The method of  claim 1 , wherein the polymer is a peptide.  
     
     
         15 . The method of  claim 1 , wherein the polymer is (K−D) n , wherein n is an integer between 10 and 100, inclusive.  
     
     
         16 . The method of  claim 1 , wherein the polymer is [K−(Xaa) m −D] n , wherein each Xaa is independently any neutral amino acid, m is an integer between 0 and 8, inclusive, and n is an integer between 1 and 100, inclusive.  
     
     
         17 . The method of  claim 1 , wherein the method further comprises administering to the subject an anti-allergy medicament selected from the group consisting of glucocorticoids, antihistamines, and anti-IgE.  
     
     
         18 . The method of  claim 1 , wherein the administering comprises administering to the subject having an allergic condition other than asthma multiple doses of the isolated polymer to treat the allergic condition.  
     
     
         19 . A method for treating a subject having an allergic condition associated with an identified allergen, comprising 
 (a) exposing a subject having an allergic condition associated with an identified allergen to the allergen; and    (b) administering to the subject an isolated polymer in an effective amount to treat the allergic condition, wherein the polymer includes repeating units of a charge motif characteristic of  B. fragilis  polysaccharide A (PSA), the motif being a positively charged free amino moiety and a negatively charged moiety selected from the group consisting of carboxyl, phosphate, phosphonate, sulfate and sulfonate.    
     
     
         20 - 22 . (canceled).  
     
     
         23 . A method for treating asthma in a subject, comprising: administering to a subject having asthma an isolated polymer in an effective amount to treat the asthma, wherein the polymer comprises repeating units of a charge motif characteristic of  B. fragilis  polysaccharide A (PSA), the motif being a positively charged free amino moiety and a negatively charged moiety selected from the group consisting of carboxyl, phosphate, phosphonate, sulfate, and sulfonate.  
     
     
         24 - 36 . (canceled).  
     
     
         37 . A method for treating a subject having asthma associated with an identified allergen, comprising 
 (a) exposing a subject having asthma associated with an identified allergen to the allergen; and    (b) administering to the subject a polymer in an effective amount to treat the asthma, wherein the polymer includes repeating units of a charge motif characteristic of  B. fragilis  polysaccharide A (PSA), the motif being a positively charged free amino moiety and a negatively charged moiety selected from the group consisting of carboxyl, phosphate, phosphonate, sulfate and sulfonate.    
     
     
         38 - 40 . (canceled).  
     
     
         41 . A method for inducing interleukin 10 (IL-10) production, comprising: 
 isolating a T regulatory cell; and    contacting the T regulatory cell with an effective amount of an isolated polymer to induce production of IL-10 by the T regulatory cell, wherein the polymer comprises repeating units of a charge motif characteristic of  B. fragilis  polysaccharide A (PSA), the motif being a positively charged free amino moiety and a negatively charged moiety selected from the group consisting of phosphate, phosphonate, sulfate, and sulfonate.    
     
     
         42 - 45 . (canceled).  
     
     
         46 . A method for inducing expression of inducible costimulatory molecule (ICOS) on a CD4+ cell, comprising: 
 contacting a CD4+ cell with an effective amount of an isolated polymer to induce expression of ICOS on the CD4+ cell, wherein the polymer comprises repeating units of a charge motif characteristic of  B. fragilis  polysaccharide A (PSA), the motif being a positively charged free amino moiety and a negatively charged moiety selected from the group consisting of carboxyl, phosphate, phosphonate, sulfate and sulfonate; and    measuring an increased ICOS expression on the CD4+ cell, wherein ICOS expression on the CD4+ cell is increased when ICOS expression after the contacting exceeds ICOS expression before the contacting.    
     
     
         47 - 56 . (canceled).  
     
     
         57 . A method for inducing proliferation of T regulatory cells, comprising 
 isolating a population of naïve T cells; and    contacting the population of naïve T cells with an effective amount of an isolated polymer to induce proliferation of T regulatory cells, wherein the polymer includes repeating units of a charge motif characteristic of  B. fragilis  polysaccharide A (PSA), the motif being a positively charged free amino moiety and a negatively charged moiety selected from the group consisting of carboxyl, phosphate, phosphonate, sulfate and sulfonate.    
     
     
         58 - 59 . (canceled).  
     
     
         60 . A method for inducing proliferation of T regulatory cells, comprising: 
 isolating a population of T regulatory cells; and    contacting the population of T regulatory cells with an effective amount of an isolated polymer to induce proliferation of the T regulatory cells, wherein the polymer comprises repeating units of a charge motif characteristic of  B. fragilis  polysaccharide A (PSA), the motif being a positively charged free amino moiety and a negatively charged moiety selected from the group consisting of carboxyl, phosphate, phosphonate, sulfate, and sulfonate.    
     
     
         61 - 66 . (canceled).  
     
     
         67 . A method for inhibiting an antigen-specific immune response in a subject, wherein the antigen-specific response is other than an allergic condition or asthma, comprising administering to a subject in need of inhibition of an antigen-specific response, other than an allergic condition or asthma, (a) an antigen and (b) an isolated polymer in an effective amount to inhibit in the subject an immune response to the antigen, wherein the polymer includes repeating units of a charge motif characteristic of  B. fragilis  polysaccharide A (PSA), the motif being a positively charged free amino moiety and a negatively charged moiety selected from the group consisting of carboxyl, phosphate, phosphonate, sulfate and sulfonate.  
     
     
         68 - 71 . (canceled).  
     
     
         72 . A composition comprising a conjugate comprising an antigen and a polymer, wherein the polymer includes repeating units of a charge motif characteristic of  B. fragilis  polysaccharide A (PSA), the motif being a positively charged free amino moiety and a negatively charged moiety selected from the group consisting of carboxyl, phosphate, phosphonate, sulfate and sulfonate.  
     
     
         73 . A pharmaceutical composition, comprising: 
 an aerosol formulation of a polymer of repeating units of a charge motif characteristic of  B. fragilis  polysaccharide A (PSA), the motif being a positively charged free amino moiety and a negatively charged moiety selected from the group consisting of carboxyl, phosphate, phosphonate, sulfate, and sulfonate.    
     
     
         74 - 92 . (canceled).  
     
     
         93 . An aerosol delivery system comprising a container with an interior, an aerosol generator in fluid connection with the interior of the container, and a pharmaceutical composition of  claim 73  disposed within the interior of the container.  
     
     
         94 - 97 . (canceled).