Immunogen

Abstract

The present invention relates, in general, to an immunogen and, in particular, to an immunogen for inducing antibodies that neutralize a wide spectrum of HIV primary isolates. The invention also relates to a method of inducing anti-HIV antibodies using same.

1 . An isolated immunogen comprising an HIV envelope protein bound to a ligand, which ligand upregulates at least one of the CD4 binding site and the CCR5 binding site on said protein.  
     
     
         2 . The immunogen according to  claim 1  when said HIV protein is gp120, uncleaved gp140 or gp120 noncovalently bound to gp41.  
     
     
         3 . The immunogen according to  claim 1  wherein said ligand is an antibody, or Fab 2  or Fab fragment thereof.  
     
     
         4 . The immunogen according to  claim 2  wherein said ligand binds to a CCR5 binding site on gp120 and upregulates a CD4 binding site on gp120.  
     
     
         5 . The immunogen according to  claim 4  wherein said ligand is an antibody, or Fab 2  or Fab fragment thereof.  
     
     
         6 . The immunogen according to  claim 4  wherein said ligand is monoclonal antibody (mab) 17b, or Fab 2  or Fab fragment thereof, or mimic thereof.  
     
     
         7 . The immunogen according to  claim 1  wherein said ligand upregulates a CCR5 and a CD4 binding site on gp120.  
     
     
         8 . The immunogen according to  claim 7  wherein said ligand is an antibody, or Fab 2  or Fab fragment thereof.  
     
     
         9 . The immunogen according to  claim 7  wherein said ligand binds to a site on gp120 to which mab A32 binds.  
     
     
         10 . The immunogen according to  claim 9  wherein said ligand is mab A32, or Fab 2  or Fab fragment thereof, or mimic thereof.  
     
     
         11 . The immunogen according to  claim 1  wherein said protein and said ligand are crosslinked.  
     
     
         12 . The immunogen according to  claim 1  wherein said protein is in soluble form.  
     
     
         13 . The immunogen according to  claim 1  wherein said protein is associated with a cell vesicle or liposome.  
     
     
         14 . The immunogen according to  claim 1  wherein said protein is gp120 noncovalently bound to gp41.  
     
     
         15 . The immunogen according to  claim 14  wherein gp120, gp41 and said ligand are crosslinked.  
     
     
         16 - 27 . (canceled)