Use of a lipopeptide or lipoprotein as an adjuvant in therapeutic or prophylactic vaccinations

Abstract

Disclosed is the use of lipopeptides and lipoproteins as mucosal adjuvants for various vaccinations via mucous membranes, particularly intranasally. Said lipopeptides represent peptides or proteins substituted with 2,3-diacyloxy(2R)-propyl at the amino-terminal cystein of a peptide or protein, preferably S-(2,3-bispalmitoyloxy-(2R)-propyl)cysteinyl peptides derived from mycoplasmas. Said peptides are highly effective even in small doses, produce good immunization results, and increase the IgA level, among others.

1 . The use of a lipopeptide or lipoprotein of the structure (I)  
       
         
           
           
               
               
           
         
       
       where 
 R 1  and R 2 , which may be identical or different, are C 7-25 -alkyl, C 7-25 -alkenyl or C 7-25 -alkynyl,  
 Xi s S, O or CH 2 ,  
 R 3  and R 4  are independently of one another H or methyl and  
 Y is a physiologically tolerated amino acid sequence which consists of 1 to 25, preferably 12 to 25, amino acid residues and is not immunogenic per se in the species used,  
 and the asymmetric carbon atom marked with * as the absolute R configuration, according to the Cahn-Inhold-Prelog rule, when X is S (sulfur),  
 as mucosal adjuvant in therapeutic or prophylactic vaccination via the mucous membranes.  
 
     
     
         2 . The use as claimed in  claim 1 , characterized in that the amino acid sequence Y is preferably selected from  
       
         
           
                 
                 
                 
                 
               
                     
                     
                 
                     
                   a) GQTNT 
                   (SEQ ID NO: 1) 
                     
                 
                     
                     
                 
                     
                   b) SKKKK 
                   (SEQ ID NO: 2) 
                 
                     
                     
                 
                     
                   c) GNNDESNISFKEK 
                   (SEQ ID NO: 3) 
                 
                     
                   and 
                 
                     
                     
                 
                     
                   d) GQTDNNSSQSAAPGSGTTNT. 
                   (SEQ ID NO: 4) 
                 
                     
                     
                 
             
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         3 . The use as claimed in  claim 1 , characterized in that the lipoprotein or lipopeptide of structure (I) is an S-[2, 3-bispalmitoyloxy(2R)propyl]cysteinyl-peptide, where the peptide is a physiologically tolerated amino acid sequence which consists of 12 to 25 amino acid residues and is preferably not immunogenic in the species used.  
     
     
         4 . The use as claimed in  claim 1 , characterized in that the mucosal adjuvant is present in a preparation with the actual vaccine component which is intended for intranasal, intra-NALT, aerosolized oral, intrarectal, conjunctival, intravaginal or intraurethral administration or administration into the milk ducts of the female breast.  
     
     
         5 . The use as claimed in  claim 1 , characterized in that the mucosal adjuvant is present in a kit for coadministration with a vaccine into the milk ducts of the female breast, by the intranasal, intra-NALT, aerosolized oral, intrarectal, conjunctival, intravaginal or intraurethral route.  
     
     
         6 . The use of a lipopeptide or lipoprotein of the general structure (I)  
       
         
           
           
               
               
           
         
       
       where  
       R 1  and R 2 , which may be identical or different, are C 7-25 -alkyl, C 7-25 -alkenyl or C 7-25 -alkynyl,  
       X is S, O or CH 2 ,  
       R 3  and R 4  are independently of one another H or methyl and  
       Y is a physiologically tolerated amino acid sequence which consists of 1 to 25, preferably 12 to 25, amino acid residues and is not immunogenic per se in the species used, and the asymmetric carbon atom market with * as the absolute R configuration, according to the Cahn-Ingold-Prelog rule, when X is S (sulfur), excepting an S-(2,3-diacyloxypropyl)cysteinpeptide of the sequence DhcGNNDESNISFKEK (SEQ ID NO: 3), where N-terminally the amino acids at positions 2 and, where appropriate, 3 are absent, and/or C-terminally 1 to 2 amino acids may be deleted, as adjuvant in a non-mucosal vaccination.  
     
     
         7 . The use as claimed in  claim 1 , characterized in that the lipopeptide or lipoprotein is present in a preparation with at least one further adjuvant and/or antigen.  
     
     
         8 . The use as claimed in  claim 1 , characterized in that the lipopeptide or lipoprotein is associated or combined with a physical or biological carrier.  
     
     
         9 . The use as claimed in  claim 1 , characterized in that the lipopeptide or lipoprotein is administered together with one or more anti-inflammatory, antiangiogenic, cytotoxic or immunomodulatory substances or ligands or with antibodies, or is present with these in a preparation.  
     
     
         10 . The use as claimed in  claim 1 , characterized in that the lipopeptide or lipoprotein is present in a preparation which comprises further additives and excipients, in particular preservatives or stabilizers.  
     
     
         11 . The use as claimed in  claim 1 , characterized in that the vaccine which is accompanied by the adjuvant, in the form of peptides, proteins, DNA, polysaccharides, glycolipids or glucoproteins.