The Caveolin-1 Binding Domain of HIV-1 Glycoprotein gp41 Is an Efficient B Cell Epitope Vaccine Candidate against Virus Infection

Abstract

Caveolin-1 is a scaffolding protein that organizes and concentrates specific ligands within the caveolae membranes. We identified a conserved caveolin-1 binding motif in the HIV-1 transmembrane envelope glycoprotein gp41 and designed several synthetic peptides, referred to as CBD1, corresponding to the consensus caveolin-1 binding domain in gp41. In rabbits, these peptides elicit the production of antibodies that inhibit infection of primary CD4(+) T lymphocytes by various primary HIV-1 isolates. Interestingly, gp41 exists as a stable complex with caveolin-1 in HIV-infected cells. Anti-CBD1 peptide antibodies, therefore, might be functional by inhibiting the potential interaction of gp41 with caveolin-1. Because of their capacity to elicit antibodies that inhibit the different clades of HIV-1, CBD1-based peptides may represent a novel synthetic universal B cell epitope vaccine candidate for HIV/AIDS. Moreover, such peptides could also have an application as a therapeutic vaccine since CBD1-specific antibodies are rare in HIV-infected individuals from several geographic origins.

A highly conserved sequence associated with the HIV gp41 loop region is an immunomodulator of antigen-specific T cells in mice

“…42 Another binding site of the Trp residues is the N-terminal part of gp41, which forms the hairpin conformation of the protein in the late fusion steps. 43 These reports further support the ability of ISLAD to interact with membrane-embedded proteins, demonstrated here by the TCR.…”

New cholesterol-specific antibodies remodel HIV-1 target cells’ surface and inhibit their in vitro virus production

“…Although cholesterol was shown to be essential to trigger events leading to membrane fusion between the target cell and the virus, it is not required for the Env-mediated membrane fusion itself ( 32 ). Interestingly, immunization with a peptide corresponding to the caveolin-1 binding domain of gp41 virus glycoprotein was able to elicit effi cient neutralizing antibodies, which act predominantly on the virus to prevent HIV-1 infection ( 33 ).…”

Endogenous adipocyte apolipoprotein E is colocalized with caveolin at the adipocyte plasma membrane

“…Binding of apoE to cav-1 was determined using a previously described approach ( 27 ). A putative aromatic amino acid enriched cav-1 binding domain in human apoE (CBDE, amino acids 41-60: GQRWELALGR FWDYLRWVQT), a biotin labeled CBDE (B-CBDE), and a mutant CBDE (CBDE-mut) in which all aromatic amino acids were changed to glycine, were synthesized by Biomatik Corp. (Ontario, Canada).…”