Compositions and methods for activating innate and allergic immunity

Abstract

Methods for making and using therapeutic formulations of Proteosome-based immunoactive compositions are provided. The immunogenic compositions, which include Proteosomes and liposaccharides, may be used to elicit or enhance a nonspecific innate immune response to, for example, treat or prevent infectious disease. In addition, after activating the innate immune system, immunogenic compositions further containing an antigen may be used to elicit a specific adaptive immune response. Furthermore, provided are compositions capable of altering hyperreactive responses or inflammatory immune responses, such as allergic reactions. Such compositions may be used as a prophylactic, or in various clinical settings to treat or prevent infectious disease (such as parasite, fungal, bacterial or viral infections), or to alter inappropriate inflammatory immune responses (such as allergic reactions or asthma).

1 . A method for eliciting a nonspecific immune response, comprising administering to a subject an immunostimulatory composition in an amount sufficient to elicit a nonspecific immune response, wherein the immunostimulatory composition comprises Proteosomes and liposaccharide. 
     
     
         2 . The method according to  claim 1  wherein the immunostimulatory composition is administered by a route selected from at least one of mucosal, enteral, parenteral, transdermal, transmucosal, nasal, and inhalation. 
     
     
         3 . The method according to  claim 2  wherein the immunostimulatory composition is administered nasally. 
     
     
         4 . The method according to  claim 1  wherein the liposaccharide final content by weight as a percentage of Proteosome protein ranges from about 1% to 500%. 
     
     
         5 . The method according to  claim 1  wherein the Proteosomes and liposaccharide are obtained from the same Gram-negative bacterial species. 
     
     
         6 . The method according to  claim 1  wherein the Proteosomes are obtained from a first Gram-negative bacterial species and the liposaccharide is obtained from a second Gram-negative bacterial species. 
     
     
         7 . The method according to  claim 1  wherein the liposaccharide is obtained from a Gram-negative bacterium selected from at least one of  Shigella  species,  Chlamydia  species,  Yersinia  species,  Pseudomonas  species,  Plesiomonas  species,  Escherichia  species,  Porphyromonas  species, and  Salmonella  species. 
     
     
         8 . The method according to  claim 1  wherein the Proteosomes are obtained from  Neisseria  species. 
     
     
         9 . The method according to  claim 1  wherein the Proteosomes are obtained from  Neisseria meningitidis,  and the liposaccharide is obtained from  Shigella flexneri.    
     
     
         10 . The method of  claim 1  wherein the method further comprises administering to the subject an immunogenic composition after administering the immunostimulatory composition, wherein the immunogenic composition comprises Proteosomes, liposaccharide, and a microbial antigen. 
     
     
         11 . The method according to  claim 10  wherein the immunogenic composition comprises at least two microbial antigens. 
     
     
         12 . The method according to  claim 10  wherein the microbial antigen is a viral antigen, a bacterial antigen, a fungal antigen, or a parasitic antigen. 
     
     
         13 . The method according to  claim 11  wherein the at least two microbial antigens are obtained from the same microorganism, wherein the microorganism is a bacterium, a virus, a fungus, or a parasite. 
     
     
         14 . The method according to  claim 11  wherein the at least two microbial antigens are obtained from different microorganisms. 
     
     
         15 . The method according to  claim 10  wherein the ratio of the weight of Proteosomes and liposaccharide of the immunogenic composition to the weight of the microbial antigen of the immunogenic composition is within a range from 4:1 to 1:4. 
     
     
         16 . The method according to  claim 10  wherein the ratio of the weight of Proteosomes and liposaccharide of the immunogenic composition to the weight of the microbial antigen of the immunogenic composition is within a range from 1:1 to 1:500. 
     
     
         17 . The method according to  claim 10  wherein the ratio of the weight of Proteosomes and liposaccharide of the immunogenic composition to the weight of the microbial antigen of the immunogenic composition is within a range from 1:1 to 1:200. 
     
     
         18 . The method according to  claim 10  wherein the microbial antigen is recombinant. 
     
     
         19 . The method according to  claim 10  wherein the microbial antigen is a bacterial antigen. 
     
     
         20 . The method according to  claim 19  wherein the bacterial antigen is obtained from  Bacillus anthracis, Chlamydia trachomatis, Yersinia pestis,  or  Enteropathogenic Escherichia coli.    
     
     
         21 . The method according to  claim 20  wherein the bacterial antigen is Protective Antigen from  Bacillus anthracis.    
     
     
         22 . The method according to  claim 10  wherein the microbial antigen of the immunogenic composition is a viral split antigen. 
     
     
         23 . The method according to  claim 22  wherein the viral split antigen is an influenza split antigen. 
     
     
         24 . The method according to  claim 10  wherein the immunogenic composition is administered about one to about ten days after the immunostimulatory composition. 
     
     
         25 . The method according to  claim 10  wherein the immunogenic composition elicits an adaptive immune response. 
     
     
         26 . The method according to  claim 1  wherein the nonspecific immune response is an innate immune response that prevents or treats a microbial infection. 
     
     
         27 . The method according to  claim 26  wherein the microbial infection is a viral, parasitic, fungal, or bacterial infection. 
     
     
         28 . The method according to either  claim 1  or  claim 10  wherein at least one of the immunostimulatory composition and the immunogenic composition further comprises a pharmaceutically acceptable carrier. 
     
     
         29 . The method according to  claim 26  wherein the microbial infection is a viral infection. 
     
     
         30 . The method according to  claim 29  wherein the viral infection is an influenza viral infection.