Identification of immunodominant epitopes in inactivated Tat-vaccinated healthy and HIV-1-infected volunteers

We analyzed the epitopes and the molecular forms of Tat recognized by the antibodies raised by Tat-toxoid vaccination in both healthy and HIV-infected volunteers. Tat-toxoid-vaccinated healthy volunteer sera reacted predominantly with peptides covering amino acids 1 through 24 and 46 through 60, corresponding to the N-terminus and basic domains of Tat. In contrast, whereas all sera from vaccinated HIV-1-positive patients reacted with the N-terminus and (with a single exception) with the basic domain, most of these sera also recognized peptides encompassing distinct domains of Tat, particularly the C-terminus (79-86). The sera of vaccinated individuals recognized both monomeric and oligomeric forms of Tat 1 through 86 or of Tat 1 through 101 and also blocked the ability of cell-released extracellular Tat to transactivate the HIV-1 LTR promoter. Synthetic Tat preincubated with sera from vaccinated individuals lost its functional activity as well. This is probably because of its inability to enter the cells as a result of immune complex formation with anti-Tat IgG. These data demonstrate that Tat-toxoid vaccination induces an efficient antibody response blocking the functional activity of Tat.