HIV inhibition by CD4 and CCR5-derived glycopeptides

We have previously proposed a method by which natural antibodies can be redirected toward a known pathogen. We could show that CD4-derived peptides coupled to the galα1,3gal sugar moiety, a specificity held by natural antibodies, were able to neutralize HIV. Importantly, the antibody-peptide-antigen complexes activated the innate immune system through the Fc parts of the natural antibody. We now tested these peptides for their effectiveness on primary isolates and included sequence variations to increase their binding affinity. In addition, we evaluated three new CCR5-derived peptides. All peptides were tested for neutralization of six primary HIV-1 isolates. When testing three of the previously published glycopeptides we found that 10 to 100 times higher concentrations were needed to achieve the same neutralization of primary isolates. We found that the modifications of the CD4 glycopeptides modestly improved the neutralization of HIV-1. The modified CD4 and the CCR5 glycopeptides neutralized HIV-1 strains from different patients and of different subtypes. Notably, the combination of CD4 and CCR5 glycopeptides enhanced the neutralization potential as compared to the single peptides. A combination of CD4- and CCR5-galα1,3gal-linked peptides redirected natural antibodies to neutralize primary isolates of HIV-1, although less efficiently than laboratory-adapted strains. This might represent a new and valuable tool to block the entry of HIV into susceptible cells.