Conformationally stabilized HIV envelope immunogens and triggering HIV-I envelope to reveal cryptic V3-loop epitopes

An isolated nucleic acid comprising a nucleotide sequence encoding a wild type HIV-1 gp120 polypeptide, or immunogenic fragment thereof, comprising substitutions of cysteines for the amino acids in at least one of residue pairs 96 and 275;

• 109 and 428;
• 123 and 431;
• and 231 and 267, and amino acid substitutions at positions 257 and 375, wherein the polypeptide, or fragment thereof further comprises a tryptophan at position 95 if the polypeptide, or fragment thereof comprises cysteines at residue pairs 96 and 275, and wherein the residue numbers correspond to amino acid positions in the amino acid sequence set forth as SEQ ID NO:
• 27.