The
CBD1 peptide (
SLEQIWNNMTWMQWDK), corresponding to the consensus
caveolin-1 binding domain in HIV-1 envelope
glycoprotein gp41 (CBD1), elicits the production of
antibodies that inhibit
infection of primary CD4(+) T lymphocytes by various primary HIV-1 isolates. Here we show that HIV-
neutralizing antibodies against CBD1 react with multiple conformational
epitopes that overlap the highly conserved
caveolin-1 binding motif (CBM) with the N-terminal conserved
isoleucine residue. The CBM-based
peptides IWNNMTWMQW and IWNNMTW when fused to a T helper
epitope are immunogenic by inducing high titer CBM-specific
antibodies capable of neutralizing HIV-1
infection in primary T lymphocyte cultures. Interestingly, neutralizing
immune sera raised against a given
peptide do not cross-react with related CBM-derived
peptides, thus suggesting the existence of distinct neutralizing
epitopes that probably reflect the dynamic conformational features of CBD1. In accord with this, the mixture of neutralizing
immune sera raised against several CBM-derived
peptides exerts a synergistic neutralizing activity against HIV-1
infection. Finally, the existence of several distinct overlapping
epitopes in CBD1 is confirmed by murine
monoclonal antibodies that we generated against the CBM-derived chimeric
peptides. Our results indicate that CBD1- and CBM-based
peptides mimic distinct dynamic conformations of CBD1, and thus such
peptides could provide specific immunogens for an efficient
vaccine preparation against HIV/
AIDS infection.