Peptide compositions for the treatment and prevention of HIV infection

Abstract

The present invention provides for peptide conjugate compositions, methods of using the peptide conjugate compositions, and pharmaceutical compositions comprising the peptide conjugate compositions. The peptide conjugate compositions comprise peptides with amino acid sequences similar to the gp 120 principal neutralizing domain (PND) of HIV, gp41, and Nef (p27) of HIV and carriers which enhance immunogenicity. The peptide conjugate compositions of the present invention may comprise a multivalent cocktail of several different peptide conjugates. Also provided by present invention is a method for reducing the level of HIV titers in a mammal by administering to the mammal a peptide composition of the present invention in an amount effective to reduce the level of HIV titers. The peptide conjugate compositions of the present invention induce prolonged antibody response in serum, a high level of antibody in the mucosa, and the production of cytotoxic lymphocytes. The peptide conjugate compositions of the present invention also elicit neutralizing antibodies and decrease viral loads in a subject.

What is claimed is:  
     
         1 . A method for reducing the level of HIV titers in a mammal comprising administering to said mammal a peptide composition in an amount effective to reduce the level of HIV titers in said mammal, wherein said peptide composition comprises at least one peptide coupled to an immunogenic carrier, and wherein said peptide is selected from the group consisting of KRIHIGPGRAFYT (SEQ ID NO:1), RSIHIGPGRAFYA (SEQ ID NO:6), KSITKGPGRVIYA (SEQ ID NO:7), KGIAIGPGRTLYA (SEQ ID NO:8), SRVTLGPGRVWYT (SEQ ID NO:9), and HIV strain variants thereof.  
     
     
         2 . The method of  claim 1 , wherein said carrier is selected from the group consisting of PPD, toxin A, filamentous hemagglutin, T helper cell epitopes of tetanus toxoid, glucoconjugate, cloned 10 kDa  M. leprae  protein, cloned 10 kDa  M. tuberculosis  protein, cloned 19 kDa  M. leprae  protein, cloned 19 kDa  M. tuberculosis  protein, cloned 30-32 kDa  M. leprae  protein and cloned 30-32 kDa  M. tuberculosis  protein.  
     
     
         3 . The method of  claim 1 , further comprising at least one peptide selected from the group consisting of LLELDKWA (SEQ ID NO:10), RPMTYK (SEQ ID NO:11), GGKWSK (SEQ ID NO:12), PGPGIRY (SEQ ID NO:13), and GPGIGPGV (SEQ ID NO: 14), and HIV strain variants thereof, wherein said peptide is coupled to an immunogenic carrier.  
     
     
         4 . The method of  claim 3 , wherein said carrier is selected from the group consisting of PPD, toxin A, filamentous hemagglutin, T helper cell epitopes of tetanus toxoid, glucoconjugate, cloned 10 kDa  M. leprae  protein, cloned 10 kDa  M. tuberculosis  protein, cloned 19 kDa  M. leprae  protein, cloned 19 kDa  M. tuberculosis  protein, cloned 30-32 kDa  M. leprae  protein and cloned 30-32 kDa  M. tuberculosis  protein.  
     
     
         5 . The method of  claim 1 , wherein the peptide composition is administered prior to HIV infection.  
     
     
         6 . The method of  claim 1 , wherein the peptide composition is administered subsequent to HIV infection.  
     
     
         7 . A peptide composition comprising at least one peptide coupled to an immunogenic carrier, wherein said peptide is selected from the group consisting of KRIHIGPGRAFYT (SEQ ID NO:1), RSIHIGPGRAFYA (SEQ ID NO:6), KSITKGPGRVIYA (SEQ ID NO:7), KGIAIGPGRTLYA (SEQ ID NO:8), SRVTLGPGRVWYT (SEQ ID NO:9), and HIV strain variants thereof.  
     
     
         8 . The peptide composition of  claim 7 , wherein said carrier is selected from the group consisting of PPD, toxin A, filamentous hemagglutin, T helper cell epitopes of tetanus toxoid, glucoconjugate, cloned 10 kDa  M. leprae  protein, cloned 10 kDa  M. tuberculosis  protein, cloned 19 kDa  M. leprae  protein, cloned 19 kDa  M. tuberculosis  protein, cloned 30-32 kDa  M. leprae  protein and cloned 30-32 kDa  M. tuberculosis  protein.  
     
     
         9 . The peptide composition of  claim 7 , further comprising at least one peptide selected from the group consisting of LLELDKWA (SEQ ID NO:10), RPMTYK (SEQ ID NO:11), GGKWSK (SEQ ID NO:12), PGPGIRY (SEQ ID. NO:13), and GPGIGPGV (SEQ ID NO:14), and HIV strain variants thereof, wherein said peptide is coupled to an immunogenic carrier.  
     
     
         10 . The peptide composition of  claim 9 , wherein said carrier is selected from the group consisting of PPD, toxin A, filamentous hemagglutin, T helper cell epitopes of tetanus toxoid, glucoconjugate, cloned 10 kDa  M. leprae  protein, cloned 10 kDa  M. tuberculosis  protein, cloned 19 kDa  M. leprae  protein, cloned 19 kDa  M. tuberculosis  protein, cloned 30-32 kDa  M. leprae  protein and cloned 30-32 kDa  M. tuberculosis  protein.  
     
     
         11 . A pharmaceutical composition comprising a peptide composition comprising at least one peptide coupled to an immunogenic carrier, wherein said peptide is selected from the group consisting of KRIHIGPGRAFYT (SEQ ID NO:1), RSIHIGPGRAFYA (SEQ ID NO:6), KSITKGPGRVIYA (SEQ ID NO:7), KGIAIGPGRTLYA (SEQ ID NO:8), SRVTLGPGRVWYT (SEQ ID NO:9), and HIV strain variants thereof, and said peptide composition is present in said pharmaceutical composition in an amount effective to reduce HIV titers in a mammal administered said pharmaceutical composition.  
     
     
         12 . The pharmaceutical composition of  claim 11 , wherein said carrier is selected from the group consisting of PPD, toxin A, filamentous hemagglutin, T helper cell epitopes of tetanus toxoid, glucoconjugate, cloned 10 kDa  M. leprae  protein, cloned 10 kDa  M. tuberculosis  protein, cloned 19 kDa  M. leprae  protein, cloned 19 kDa  M. tuberculosis  protein, cloned 30-32 kDa  M. leprae  protein and cloned 30-32 kDa  M. tuberculosis  protein.  
     
     
         13 . The pharmaceutical composition of  claim 12 , further comprising at least one peptide selected from the group consisting of LLELDKWA (SEQ ID NO:10), RPMTYK (SEQ ID NO:11), GGKWSK (SEQ ID NO:12), PGPGIRY (SEQ ID NO:13), and GPGIGPGV (SEQ ID NO:14), and HIV strain variants thereof, wherein said peptide is coupled to an immunogenic carrier.  
     
     
         14 . The pharmaceutical composition of  claim 13 , wherein said carrier is selected from the group consisting of PPD, toxin A, filamentous hemagglutin, T helper cell epitopes of tetanus toxoid, glucoconjugate, cloned 10 kDa  M. leprae  protein, cloned 10 kDa  M. tuberculosis  protein, cloned 19 kDa  M. leprae  protein, cloned 19 kDa  M. tuberculosis  protein, cloned 30-32 kDa  M. leprae  protein and cloned 30-32 kDa  M. tuberculosis  protein.