Schematic representation of the prime-boost strategy. The fragment immunogen carrying the b12 binding site exists in equilibrium between the folded and partially folded forms. As shown in A, upon priming with the fragment immunogen, antibodies (red) elicited against the partially folded forms predominate. Upon boosting with full-length gp120, the cross-reactive antibodies (orange-encircled ones directed toward the CD4 binding site and blue ones directed toward regions other than the CD4bs) are selectively amplified, resulting in increasing amounts of CD4 binding site antibodies. B, a conventional gp120 prime/gp120 boost immunization, where lower levels of CD4 binding site antibodies (orange-encircled ones) are produced.