Microbial delivery system

Abstract

The present invention provides methods and compositions for treating or preventing allergic responses, particularly anaphylactic allergic responses, in subjects who are allergic to allergens or susceptible to allergies. Methods of the present invention utilize administration of microorganisms to subjects, where the microorganisms produce allergens and protect the subjects from exposure to the allergens until phagocytosed by antigen-presenting cells. Particularly preferred microorganisms are gram-negative bacteria, gram-positive bacteria, and yeast. Particularly preferred allergens are proteins found in foods, venoms, drugs and latex that elicit allergic reactions and anaphylactic allergic reactions in individuals who are allergic to the proteins or are susceptible to allergies to the proteins. The proteins may also be modified to reduce the ability of the proteins to bind and crosslink IgE antibodies and thereby reduce the risk of eliciting anaphylaxis without affecting T-cell mediated Th1-type immunity.

We claim:  
     
         1 - 33 . (Cancelled)  
     
     
         34 . A composition comprising: 
 dead  E. coli  containing therein at least one modified allergen whose amino acid sequence differs from that of a wild-type allergen that occurs in nature such that the modified allergen has a reduced ability to bind to or cross-link IgE as compared with the wild-type allergen; and    a pharmaceutically acceptable carrier.    
     
     
         35 . The composition of  claim 34 , wherein the wild-type allergen is found in nature in foods, venoms, or latex.  
     
     
         36 . The composition of  claim 34 , wherein the wild-type allergen is found in nature in a food selected from the group consisting of peanuts, milk, eggs, seafood, nuts, dairy products, and fruit.  
     
     
         37 . The composition of  claim 34 , wherein the wild-type allergen is found in nature in bee venom.  
     
     
         38 . The composition of  claim 34 , wherein the wild-type allergen is Ara h 1 (SEQ ID NO:1), Ara h 2 (SEQ ID NO:2), or Ara h 3 (SEQ ID NO:3).  
     
     
         39 . The composition of  claim 34 , wherein the sequence of the modified allergen differs from the sequence of the wild-type allergen by one or more amino acid deletions, substitutions or additions within an IgE binding site of the wild-type peanut allergen.  
     
     
         40 . The composition of  claim 39 , wherein the sequence of the modified allergen lacks a portion of the wild-type allergen sequence, and wherein said portion includes an IgE binding site.  
     
     
         41 . The composition of  claim 34 , wherein the modified allergen is located in the cytoplasm of the dead  E. coli.    
     
     
         42 . The composition of  claim 34 , wherein the modified allergen is located in the periplasm of the dead  E. coli.    
     
     
         43 . The composition of  claim 34 , wherein the modified allergen cannot be detected by antibody binding without disrupting the dead  E. coli.    
     
     
         44 . The composition of  claim 34 , wherein the composition is formulated for rectal administration.