novel proteosome-liposaccharide vaccine adjuvant

Abstract

An adjuvant complex composed of bacterial outer membrane protein proteosomes complexed to bacterial liposaccharide is prepared to contain the component parts under a variety of conditions. The complex can be formulated with antigenic material to form immunogenic compositions, vaccines and immunotherapeutics. An induced immune response includes protective antibodies and/or type 1 cytokines is shown for a variety of protocols.

1 .- 33 . (canceled) 
     
     
         34 . A process for preparing an immunogenic composition comprising mixing a proteosome-lipopolysaccharide adjuvant with an antigen to form the composition, wherein the proteosome-lipopolysaccharide adjuvant is formed from an outer membrane proteosome complexed with a lipopolysaccharide preparation, wherein both the proteosome and the lipopolysaccharide preparation are from gram-negative bacteria, which proteosome-lipopolysaccharide adjuvant has a final lipopolysaccharide content by weight as a percentage of the total proteosome protein of at least 13%. 
     
     
         35 . The process of  claim 34  wherein the antigen is selected from a peptide, a protein, a toxoid, a glycoprotein, a glycolipid, a lipid, a carbohydrate, and a polysaccharide. 
     
     
         36 . The process of  claim 34  wherein the antigen is derived from a biologic or infectious organism of the animal or plant kingdom, is an allergen or a chemically or biologically modified allergen, or is a chemical material. 
     
     
         37 . The process of  claim 34  wherein the antigen is whole or disrupted microorganisms selected from viruses, bacteria and parasites, attenuated and/or inactivated. 
     
     
         38 . The process of  claim 34  wherein the antigen is produced by a synthetic or a recombinant molecular procedures. 
     
     
         39 . The process of  claim 34  wherein the antigen is Bet v 1a. 
     
     
         40 . The process of  claim 34  wherein the antigen is rBet v 1a. 
     
     
         41 . The process of  claim 34  wherein the antigen is recombinant influenza antigen. 
     
     
         42 . The process of  claim 34  wherein the antigen is influenza split antigen. 
     
     
         43 . The process of  claim 34  wherein the antigen is birch pollen extract. 
     
     
         44 . The process of  claim 34  wherein the antigen is an immunogen extract. 
     
     
         45 .- 54 . (canceled) 
     
     
         55 . The process according to  claim 34  wherein the proteosome-lipopolysaccharide adjuvant is prepared by a process comprising mixing an outer membrane protein proteosome preparation prepared from a first gram-negative bacteria and a lipopolysaccharide preparation derived from a second gram-negative bacteria to effect complexing of the outer membrane protein proteosome and the lipopolysaccharide to form the proteosome-lipopolysaccharide adjuvant. 
     
     
         56 . The process of  claim 55  wherein the first gram-negative bacteria and the second gram-negative bacteria are the same. 
     
     
         57 . The process of  claim 55  wherein the first gram-negative bacteria and the second gram-negative bacteria are the different. 
     
     
         58 . The process of  claim 55  wherein the first gram-negative bacteria is selected from genus  Neisseria.    
     
     
         59 . The process of  claim 58  wherein the  Neisseria  is  Neisseria meningitidis.    
     
     
         60 . The process of  claim 55  wherein the second gram-negative bacteria is selected from the genera  Escherichia, Shigella, Plesiomonas , and  Salmonella.    
     
     
         61 . The process of  claim 60  wherein the second gram-negative bacteria is selected from  E. coli, S. flexneri, P. shigelloides , and  S. essens.    
     
     
         62 . The process of  claim 55  wherein the outer membrane protein proteosome preparation and the lipopolysaccharide preparation are mixed in a detergent solution. 
     
     
         63 . The process of  claim 62  wherein the detergent solution is EMPIGEN® BB, TRITON X-100, MEGA-10. 
     
     
         64 . The process of  claim 62  further comprising removing detergent by a dialysis, a diafiltration, or an ultrafiltration methodology or combinations thereof. 
     
     
         65 . The process of  62  further comprising removing detergent by a diafiltration or an ultrafiltration methodology or a combination thereof. 
     
     
         66 . The process of  claim 55  wherein the mixing includes co-precipitation and/or lyophilization of both preparations.