Beta-glycolipids for use as adjuvants

Abstract

The present invention relates to beta-glycolipid derivatives, their preparation and use as adjuvants in vaccines, as being suitable for being co-administered with antigens for vaccine prophylaxis and therapy. In certain embodiments, the beta-glycol-lipid derivatives of the invention also in their salified or complex form, are suitable for being co-administered with antigens for both therapeutic and prophylactic purposes or for vaccine prophylaxis and therapy.

1 . A vaccine adjuvant comprising at least one beta-glycolipid derivative of formula (I): 
       
         
           
           
               
               
           
         
         a salt or a metal complex thereof, 
         wherein 
         the acetalic bond of the anomeric carbon has β (beta) configuration, 
         A 1  and A 2  are, independently of each other, saturated or monounsaturated linear or branched C 1 -C 30  alkyl, or are an acyl —(CO)R 1  and —(CO)R 2  respectively where R 1  and R 2  are, independently of each other, saturated or monounsaturated linear or branched C 1 -C 29  alkyl, and 
         X is a sulphonic (—SO 3 H), sulphuric (—OSO 3 H), phosphoric (—OPO 3 H 2 ), or phosphonic (—PO 3 H 2 ) group. 
       
     
     
         2 . The vaccine adjuvant of  claim 1 , wherein, in the beta-glycolipid derivative, A 1  and A 2  or R 1  and R 2  are, independently of each other, saturated or monounsaturated linear C 6 -C 24  alkyl. 
     
     
         3 . The vaccine adjuvant of  claim 2 , wherein, in the beta-glycolipid derivative, A 1  and A 2  or R 1  and R 2  are, independently of each other, moieties of lauric acid, myristic acid, palmitic acid, stearic acid, arachidic acid, behenic acid or lignoceric acid. 
     
     
         4 . The vaccine adjuvant of  claim 2 , wherein, in the beta-glycolipid derivative, A 1  and A 2  or R 1  and R 2  are, independently of each other, saturated or monounsaturated linear C 14 -C 18  alkyl. 
     
     
         5 . The vaccine adjuvant of  claim 1 , wherein, in the beta-glycolipid derivative, A 1  and A 2  are acyl —(CO)R 1  and acyl —(CO)R 2  respectively, where R 1  and R 2  are, independently of each other, a moiety of pentadecanoic acid, palmitic acid, heptadecanoic acid, or stearic acid. 
     
     
         6 . The vaccine adjuvant of  claim 1 , wherein the beta-glycolipid derivative of formula (I) is in the form of a salt thereof, wherein X is a —SO 3   − , —OSO 3   − , —OPO 3   2− , —PO 2   2− , alkali or alkaline-earth metal group. 
     
     
         7 . The vaccine adjuvant of  claim 1 , wherein, in the beta-glycolipid derivative, X is —SO 3 H, —SO 3 Na, or —SO 3 K. 
     
     
         8 . The vaccine adjuvant of  claim 1 , wherein the beta-glycolipid derivative of formula (I) is in the form of a complex thereof with aluminium. 
     
     
         9 . The vaccine adjuvant of  claim 1 , said beta-glycolipid derivative being sodium or potassium salt of 1,2-diacyl-3-[1′β-(6-sulpho)-quinovosyl]-glycerol. 
     
     
         10 . The vaccine adjuvant of  claim 1 , said beta-glycolipid derivative being 1,2-distearoyl-3-[1′β-(6-sulpho)-quinovosyl]-glycerol. 
     
     
         11 . The vaccine adjuvant of  claim 1 , said beta-glycolipid derivative being 1,2-dipalmitoyl-3-[1′β-(6-sulpho)-quinovosyl]-glycerol. 
     
     
         12 . The vaccine adjuvant of  claim 1 , said beta-glycolipid derivative being 1-palmitoyl-2-stearoyl-3-[1′β-(6-sulpho)-quinovosyl]-glycerol or 1-stearoyl-2-palmitoyl-3-[1′β-(6-sulpho)-quinovosyl]-glycerol. 
     
     
         13 . The vaccine adjuvant of  claim 1  comprising at least one beta-glycolipid derivative of formula (I), a pharmaceutically acceptable salt or metal complex thereof. 
     
     
         14 . Product, composition or kit containing the vaccine adjuvant of  claim 1 , and an antigen or vaccine as combined preparation for simultaneous, separate or sequential administration for preventing or treating infectious diseases. 
     
     
         15 . A method for enhancing and/or modulating the immune response following the administration of an antigen or a vaccine to a subject in need thereof, said method comprising the administration of the vaccine adjuvant of  claim 1  optionally in co-administration with an antigen against which the subject in need thereof has to be immunized. 
     
     
         16 . The method of  claim 15 , wherein the administration of the vaccine adjuvant of  claim 1  is for treating or preventing bacterial or viral infections.