Methods and compositions for preventing or retarding the development of a atherosclerotic lesions

Abstract

A method for preventing or retarding the development atherosclerotic lesions or restenosis involves administering to a subject, preferably a human, an effective amount of an anti-viral composition directed against CMV, and optionally an anti-microbial composition directed against C. pneumoniae . These compositions may be conventional chemical anti-microbial pharmaceutics. Alternatively, the compositions may contain a cytomegalovirus (CMV) protein or fragment thereof (or nucleic acid containing compositions expressing such protein or fragment). Such compositions may contain an immunogenic C. pneumoniae protein or fragment thereof (or nucleic acid containing compositions expressing such protein or fragment). The protein/nucleic acid compositions are administered in an amount capable of inducing cell mediated immunity and/or antibody response in the subject.

What is claimed is:  
     
         1 . A method for preventing or retarding the development of atherosclerotic lesions or restenosis in a mammal comprising: 
 administering to said mammal an effective amount of a composition comprising a human cytomegalovirus (HCMV) protein or fragment thereof, said amount inducing cell mediated immunity or cell mediated immunity and antibody response in said mammal.    
     
     
         2 . The method according to    claim 1    wherein said composition is an attenuated, live HCMV.  
     
     
         3 . The method according to    claim 2    wherein said amount is a low dose comprising of between 10 3  and 10 7  pfu per inoculation.  
     
     
         4 . The method according to    claim 1    wherein said composition is an inactivated, HCMV.  
     
     
         5 . The method according to    claim 1    wherein said composition consists of a protein of HCMV and wherein said protein is selected from the group consisting of HCMV proteins pp65, IE, pp150, gB, gH, pp28, and pp52.  
     
     
         6 . The method according to    claim 5    wherein said amount is a low dose comprising of between about 10 and about 80 mgs viral protein per inoculation.  
     
     
         7 . The method according to    claim 1    further comprising: 
 co-administering to said mammal an effective amount of a composition comprising an immunogenic  Chlamydia pneumoniae  protein or fragment thereof, said amount inducing cell mediated immunity or cell mediated immunity and antibody response in said mammal.  
 
     
     
         8 . The method according to    claim 7   , wherein said co-administering step occurs before, during or after said administering of said HCMV composition.  
     
     
         9 . The method according to    claim 1    further comprising: 
 co-administering to said mammal an effective amount of an anti-microbial agent effective against  Chlamydia pneumoniae  infection.  
 
     
     
         10 . The method according to    claim 9   , wherein said co-administering step occurs before, during or after said administering of said HCMV composition.  
     
     
         11 . The method according to    claim 9   , wherein said anti-microbial agent comprises a chemical composition which kills  C. pneumoniae  in vivo.  
     
     
         12 . A method for preventing or retarding the development of atherosclerotic lesions or restenosis in a mammal comprising: 
 administering to said mammal an effective amount of a composition comprising a nucleic acid sequence encoding a human cytomegalovirus (HCMV) protein or fragment thereof, said composition inducing cell mediated immunity and/or an antibody response upon expression of said protein in said mammal.    
     
     
         13 . The method according to    claim 12    wherein said composition comprises a virus vector comprising a nucleic acid sequence encoding said protein or fragment under the control of a regulatory sequence capable of directing expression of said HCMV protein sequence.  
     
     
         14 . The method according to    claim 12    wherein said vector is a virus selected from the group consisting of adenovirus, poxvirus, and retrovirus.  
     
     
         15 . The method according to    claim 12    wherein said sequence is selected from the group consisting of a sequence encoding HCMV proteins pp65, IE, pp150, pp28, gB, gH and pp52.  
     
     
         16 . The method according to    claim 12    wherein said amount is a low dose comprising of between 50 and 200 μg of DNA per inoculation.  
     
     
         17 . The method according to    claim 12   , further comprising the step of co-administering to said mammal an effective amount of a composition comprising a nucleic acid sequence encoding an immunogenic  C. pneumoniae  protein or fragment thereof, said composition inducing cell mediated immunity and/or an antibody response upon expression of said protein in said mammal.  
     
     
         18 . The method according to    claim 17   , wherein said co-administering step occurs before, during or after said administering of said HCMV composition.  
     
     
         19 . The method according to    claim 12    further comprising: 
 co-administering to said mammal an effective amount of an anti-microbial agent effective against  Chlamydia pneumoniae  infection.  
 
     
     
         20 . The method according to    claim 19   , wherein said co-administering step occurs before, during or after said administering of said HCMV composition.  
     
     
         21 . The method according to    claim 19   , wherein said anti-microbial agent comprises a chemical composition which kills  C. pneumoniae  in vivo.  
     
     
         22 . A method for preventing or retarding the development of atherosclerotic lesions or restenosis in a mammal comprising: 
 administering to said mammal an effective amount of a composition comprising an immunogenic  Chlamydia pneumoniae  protein or fragment thereof, said amount inducing cell mediated immunity or cell mediated immunity and antibody response in said mammal.    
     
     
         23 . The method according to    claim 22    wherein said composition is an attenuated, live  C. pneumoniae.    
     
     
         24 . The method according to    claim 22    wherein said composition is an inactivated,  C. pneumoniae.    
     
     
         25 . The method according to    claim 22    wherein said amount is a low dose comprising of between about 10 and about 80 mgs protein per inoculation.  
     
     
         26 . The method according to    claim 22    further comprising: 
 co-administering to said mammal an effective amount of an anti-viral agent effective against HCMV infection.  
 
     
     
         27 . The method according to    claim 22   , wherein said co-administering step occurs before, during or after said administering of said  C. pneumoniae  composition.  
     
     
         28 . A method for preventing or retarding the development of atherosclerotic lesions or restenosis in a mammal comprising: 
 administering to said mammal an effective amount of a composition comprising a nucleic acid sequence encoding an immunogenic  C. pneumoniae  protein or fragment thereof, said composition inducing cell mediated immunity and/or an antibody response upon expression of said protein in said mammal.    
     
     
         29 . The method according to    claim 28    wherein said composition comprises a virus vector comprising a nucleic acid sequence encoding said protein or fragment under the control of a regulatory sequence capable of directing expression of said  C. pneumoniae  protein sequence.  
     
     
         30 . The method according to    claim 29    wherein said vector is a virus selected from the group consisting of adenovirus, poxvirus, and retrovirus.  
     
     
         31 . The method according to    claim 28    wherein said amount is a low dose comprising of between 50 and 200 μg of DNA per inoculation.  
     
     
         32 . The method according to    claim 28    further comprising: 
 co-administering to said mammal an effective amount of an anti-viral agent effective against HCMV infection.  
 
     
     
         33 . The method according to    claim 28   , wherein said co-administering step occurs before, during or after said administering of said  C. pneumoniae  composition.  
     
     
         34 . A method for preventing or retarding the development of atherosclerotic lesions or restenosis in a mammal comprising administering to said mammal an amount of an anti-microbial composition effective to reduce or eliminate  C. pneumoniae  infection.  
     
     
         35 . The method according to    claim 34    wherein said composition further comprises an anti-viral agent directed against HCMV.  
     
     
         36 . The method according to    claim 34   , wherein said anti-microbial agent comprises a chemical composition which kills  C. pneumoniae  in vivo.  
     
     
         37 . A composition useful for preventing or retarding the development of atherosclerotic lesions or restenosis in a mammal comprising, in a suitable pharmaceutical carrier,: 
 (a) an amount of an anti-microbial composition effective to reduce or eliminate  C. pneumoniae  infection; and    (b) an amount of an anti-viral composition effective to reduce or eliminate HCMV infection.    
     
     
         38 . The composition according to    claim 38    wherein said composition (a) is selected from the group consisting of: 
 i. a chemical composition which kills  C. pneumoniae  in vivo;  
 ii. a composition comprising an immunogenic  Chlamydia pneumoniae  protein or fragment thereof, said amount inducing cell mediated immunity or cell mediated immunity and antibody response directed against said  C. pneumoniae  in a mammal; and  
 iii. a nucleic acid sequence encoding an immunogenic  C. pneumoniae  protein or fragment thereof, said composition inducing cell mediated immunity and/or an antibody response directed against  C. pneumoniae  upon expression of said protein in a mammal.  
 
     
     
         39 . The composition according to    claim 38    wherein said composition (b) is selected from the group consisting of: 
 i. an anti-viral chemical reagent;  
 ii. a composition comprising an HCMV protein or fragment thereof, said amount inducing cell mediated immunity or cell mediated immunity and antibody response directed against said HCMV in a mammal; and  
 iii. a nucleic acid sequence encoding an HCMV protein or fragment thereof, said composition inducing cell mediated immunity and/or an antibody response directed against HCMV upon expression of said protein in a mammal.