Methods and compositions for impairing multiplication of HIV-1

Abstract

A composition which elicits antibodies to multiple known variants of Tat protein of HIV-1 of both the B and non-B clades contains the peptide R1-Asp-Pro-Asn-Leu-Asp-Pro-Trp-Asn-R2 SEQ ID NO: 23, and preferably an additional at least two variants of a peptide or polypeptide of the formula: R1-Asp-Pro-Y 7 -Leu-X 9 -Pro-Trp-Z 12 -R2 (SEQ ID NO: 8). In this composition, at least one of the two variants contains Arg at Y 7 and Lys at Z 12 , and in at least a second of the two variants Y 7 is Asn and Z 12 is Asn. Vaccinal and pharmaceutical compositions can contain one or more such peptides associated with carrier proteins, associated in multiple antigenic peptides or as part of recombinant proteins. Diagnostic compositions and uses are described for assessing the immune status of vaccinated patients.

What is claimed is:  
     
         1 . A composition comprising a nucleic acid sequence encoding an epitope located within the amino acid sequence 
       R1-Asp-Pro-Asn-Leu-Asp-Pro-Trp-Asn-R2 SEQ ID NO: 23, wherein R1 is selected from the group consisting of a sequence of between 1 to about 5 amino acids; and    wherein R2 is selected from the group consisting of a sequence of one or up to about 5 additional amino acids,    wherein said amino acid epitope induces antibodies that bind to HIV-1 Tat proteins from different HIV-1 strains and subtypes.    
     
     
         2 . The composition according to  claim 1 , wherein R1 is Val.  
     
     
         3 . The composition according to  claim 1 , wherein R1 is X-Pro-Val, wherein X is selected from the group consisting of Glu and Asp.  
     
     
         4 . The composition according to  claim 1 , wherein R2 is -His-Pro-Gly-Ser-.  
     
     
         5 . The composition according to  claim 1 , wherein said nucleic acid sequence encodes said selected epitope sequence in an open reading frame with, or fused to, at least one additional nucleic acid sequence.  
     
     
         6 . The composition according to  claim 5 , wherein said additional nucleic acid sequence encodes a carrier protein.  
     
     
         7 . The composition according to  claim 5 , wherein said additional nucleic acid sequence encodes an epitope of an HIV-1 Tat protein, said epitope located within the amino acid sequence R3-Asp-Pro-Y-Leu-Glu-Pro-Trp-Z-R4 SEQ ID NO: 8, wherein Y is selected from the group consisting of Arg, Lys, Ser and Asn, wherein Z is selected from the group consisting of Lys and Asn, wherein R3 is selected from the group consisting of a sequence of between 1 to about 5 amino acids; wherein R4 is selected from the group consisting of a sequence of one or up to about 5 additional amino acids.  
     
     
         8 . The composition according to  claim 7 , comprising from one to four different said additional nucleic acid sequences, said additional sequences encoding three different Y variants of the epitope defined by said SEQ ID NO: 8.  
     
     
         9 . The composition according to  claim 7 , comprising from one to four different said additional nucleic acid sequences, said said additional sequences encoding all four different Y variants of the epitope defined by said SEQ ID NO: 8.  
     
     
         10 . The composition according to  claim 7 , wherein R3 is selected from the group consisting of Val-, and X 1 -Pro-Val, wherein X 1  is selected from the group consisting of Glu and Asp.  
     
     
         11 . The composition according to  claim 7 , wherein R4 is -His-Pro-Gly-Ser-.  
     
     
         12 . The composition according to  claim 5 , wherein said additional nucleic acid sequence encodes an epitope sequence 
 R3-Asp-Pro-Arg-Leu-Glu-Pro-Trp-Lys-R4 SEQ ID NO: 17, and said additional nucleic acid sequence encodes an epitope sequence    R3-Asp-Pro-Asn-Leu-Glu-Pro-Trp-Asn-R4 SEQ ID NO: 18.    
     
     
         13 . The composition according to  claim 5 , wherein said additional nucleic acid sequence encodes at least one epitope sequence selected from the group consisting of:  
       
         
           
                 
                 
                 
                 
               
                     
                     
                 
                     
                   SEQ ID NO: 19 
                     
                     
                 
                 
                 
                 
               
                     
                   R3-Asp-Pro-Lys-Leu-Glu-Pro-Trp-Lys-R4 
                     
                 
                     
                     
                 
                 
                 
                 
                 
               
                     
                   SEQ ID NO: 22 
                     
                     
                 
                 
                 
                 
               
                     
                   R3-Asp-Pro-Lys-Leu-Glu-Pro-Trp-Asn-R4 
                     
                 
                     
                     
                 
                 
                 
                 
                 
               
                     
                   SEQ ID NO: 20 
                     
                     
                 
                 
                 
                 
               
                     
                   R3-Asp-Pro-Ser-Leu-Glu-Pro-Trp-Lys-R4 
                     
                 
                     
                     
                 
                 
                 
                 
                 
               
                     
                   SEQ ID NO: 24 
                     
                     
                 
                 
                 
                 
               
                     
                   R3-Asp-Pro-Ser-Leu-Glu-Pro-Trp-Asn-R4 
                     
                 
                     
                   and 
                 
                     
                     
                 
                 
                 
                 
                 
               
                     
                   SEQ ID NO: 21 
                     
                     
                 
                 
                 
                 
               
                     
                   R3-Asp-Pro-Asn-Leu-Glu-Pro-Trp-Lys-R4. 
                     
                 
                     
                     
                 
             
                
                
               
            
             
                
                
               
            
             
                
               
            
             
                
                
               
            
             
                
               
            
             
                
                
               
            
             
                
               
            
             
                
                
                
               
            
             
                
               
            
             
                
                
               
            
           
         
       
     
     
         14 . The composition according to  claim 5 , wherein said additional nucleic acid sequence encodes an epitope located within the amino acid sequence -Lys-X 1 -Leu-Gly-Ile-Ser-Tyr-Gly-Arg-Lys- of SEQ ID NO:10, wherein said amino acid X 1  is Gly or Ala.  
     
     
         15 . The composition according to  claim 1 , wherein said nucleic acid sequence further comprises at least one regulatory nucleic acid sequence operatively linked to said epitope-encoding nucleic acid sequence, which regulatory sequence directs and controls expression of at least one said amino acid sequence encoded thereby in a host cell.  
     
     
         16 . The composition according to  claim 1 , wherein said nucleic acid sequence encodes multiple copies of the same amino acid sequence.  
     
     
         17 . The composition according to  claim 1 , wherein said nucleic acid sequence encodes multiple different said amino acid sequences.  
     
     
         18 . The composition according to  claim 1 , wherein said nucleic acid sequence further encodes a spacer sequence interposed between each amino acid sequence.  
     
     
         19 . The composition according to  claim 1 , which is a plasmid.  
     
     
         20 . The composition according to  claim 1 , which is a recombinant virus non-pathogenic to humans.  
     
     
         21 . The composition according to  claim 1 , which is transfected in a commensal bacterium non-pathogenic to humans.  
     
     
         22 . The composition according to  claim 1 , further comprising a pharmaceutical carrier and an optional adjuvant.  
     
     
         23 . The composition according to  claim 22 , which is a DNA vaccine.  
     
     
         24 . The composition according to  claim 1 , wherein said nucleic acid sequence encodes sequentially at least two amino acid sequences or fragments thereof, wherein each said at least two amino acid sequences or fragments induce antibodies that bind to HIV-1 Tat proteins from different HIV-1 strains and subtypes.  
     
     
         25 . A method of inducing an immune response in a mammal comprising administering to said mammal an effective amount of a composition of  claim 1.