Composition for the treatment of atherosclerosis

Abstract

Epitopes derived from a protein present in an atherosclerotic plaque, such as apolipoprotein B-100, are presented. The epitopes can be used in a method of treating atherosclerosis by continuous subcutaneous or transcutaneous administration of a therapeutically effective amount of the epitope to a subject. Administering the epitope to the subject can induce a specific regulatory immune response, such as a Treg response. A composition or patch containing the epitope and adapted for the prophylactic or therapeutic treatment of a subject are also presented.

1 . A method for treating atherosclerosis in a subject, comprising a continuous subcutaneous or transcutaneous administration to the subject of a therapeutically effective amount of at least one epitope,
 wherein the at least one epitope is administered for a period of time and at a daily dose that are sufficient to induce a specific regulatory immune response, the at least one epitope being administered for a period of time within a range of 7 to 30 days and at a daily dose within a range of 0.05 to 5000 μg per kg body weight per day,   the epitope is a synthetic peptide derived from apolipoprotein B-100 (apoB-100), and   the synthetic peptide is selected from the group consisting of:   
       
         
           
                 
                 
               
                     
                   (SEQ ID NO: 1) 
                 
                     
                   FLDTVYGNCSTHFTVKTRKG; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 2) 
                 
                     
                   PQCSTHILQWLKRVHANPLL; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 3) 
                 
                     
                   VISIPRLQAEARSEILAHWS; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 4) 
                 
                     
                   KLVKEALKESQLPTVMDFRK; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 5) 
                 
                     
                   LFVTQAEGAKQTEATMTFK; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 6) 
                 
                     
                   DGSLRHKFLDSNIKFSHVEK; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 7) 
                 
                     
                   KGTYGLSCQRDPNTGRLNGE; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 8) 
                 
                     
                   RLNGESNLRFNSSYLQGTNQ; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 9) 
                 
                     
                   SLTSTSDLQSGIIKNTASLK; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 10) 
                 
                     
                   TASLKYENYELTLKSDTNGK; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 11) 
                 
                     
                   DMTSFKQNALLRSEYQADYE; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 12) 
                 
                     
                   MKVKIIRTIDQMQNSELQWP; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 13) 
                 
                     
                   IALDDAKINFNEKLSQLQTY; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 14) 
                 
                     
                   KTTKQSFDLSVKAQYKKNKH; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 15) 
                 
                     
                   EEEMLENVSLVCPKDATRFK; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 16) 
                 
                     
                   GSTSHHLVSRKSISAALEHK; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 17) 
                 
                     
                   IENIDFNKSGSSTASWIQNV; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 18) 
                 
                     
                   IREVTQRLNGEIQALELPQK; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 19) 
                 
                     
                   EVDVLTKYSQPEDSLIPFFE; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 20) 
                 
                     
                   HTFLIYITELLKKLQSTTVM; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 21) 
                 
                     
                   LLDIANYLMEQIQDDCTGDE; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 22) 
                 
                     
                   CTGDEDYTYKIKRVIGNMGQ; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 23) 
                 
                     
                   GNMGQTMEQLTPELKSSILK; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 24) 
                 
                     
                   SSILKCVQSTKPSLMIQKAA; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 25) 
                 
                     
                   IQKAAIQALRKMEPKDKDQE; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 26) 
                 
                     
                   RLNGESNLRFNSSYLQGTNQ; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 27) 
                 
                     
                   SLNSHGLELNADILGTDKIN; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 28) 
                 
                     
                   WIQNVDTKYQIRIQIQEKLQ; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 29) 
                 
                     
                   TYISDWWTLAAKNLTDFAEQ; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 30) 
                 
                     
                   EATLQRIYSLWEHSTKNHLQ; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 31) 
                 
                     
                   ALLVPPETEEAKQVLFLDTV; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 32) 
                 
                     
                   IEIGLEGKGFEPTLEALFGF; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 33) 
                 
                     
                   SGASMKLTTNGRFREHNAKF; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 34) 
                 
                     
                   NLIGDFEVAEKINAFRAKVH; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 35) 
                 
                     
                   GHSVLTAKGMALFGEGKAEF; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 36) 
                 
                     
                   FKSSVITLNTNAELFNQSDI; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 37) 
                 
                     
                   FPDLGQEVALNANTKNQKIR; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 38) 
                 
                     
                   ATRFKHLRKYTYNYQAQSSS; 
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
       and
 any of SEQ ID NO: 1-38 modified to mimic a modification of apoB-100 protein that may occur during oxidation or non-oxidative modification of LDL, selected from the group consisting of oxidation by exposure to copper, oxidation after aldehyde-modification or acetylation. 
 
     
     
         2 . The method according to  claim 1 , wherein the subject has been diagnosed as presenting one of the following coronary disorders:
 an asymptomatic coronary artery coronary disease with silent ischemia or without ischemia;   a chronic ischemic disorder without myocardial necrosis;   an acute ischemic disorder with myocardial necrosis; and   an ischemic disorder with myocardial necrosis.   
     
     
         3 . The method according to  claim 1 , wherein the at least one epitope is administered for a period of time within the range of 10 days to 20 days. 
     
     
         4 . The method according to  claim 1 , wherein the at least one epitope is administered at a daily dose within the range of 0.5 to 1000 μg per kg body weight per day. 
     
     
         5 . The method according to  claim 2 , wherein the chronic ischemic disorder without myocardial necrosis is stable or effort angina pectoris. 
     
     
         6 . The method according to  claim 2 , wherein the acute ischemic disorder with myocardial necrosis is unstable angina pectoris. 
     
     
         7 . The method according to  claim 2 , wherein the ischemic disorder with myocardial necrosis is ST segment elevation myocardial infarction or non-ST segment elevation myocardial infarction.