Tat-neutralizing versus Tat-protecting antibodies in rhesus macaques vaccinated with Tat peptides

The human immunodeficiency virus (HIV) regulatory protein Tat represents an attractive target for developing vaccine strategies. Both humoral and cellular responses against Tat might reduce disease progression by interfering with the deleterious functions of extracellularly secreted protein and by reducing viral replication. We have immunized Rhesus macaques intramuscularly and intranasally with a cocktail of three Tat peptides encompassing residues 1-20, 1-61 and 44-61 administrated in the presence of Montanide ISA 720 as adjuvant. The monkeys were challenged by the intrarectal route with 10 MID50 of SHIV BX08. All immunized macaques but one gave a good cross-reactive antibody response to Tat but the proliferative response and levels of IL-2, IFN-gamma and TNF-alpha secretion of peripheral blood mononuclear cells (PBMCs) recalled ex vivo with active Tat protein were weak. After viral challenge one peptide-vaccinated macaque only remained free of virus. The presence in the serum of vaccinated animals of neutralizing antibodies able to inhibit Tat transactivation activity or Tat-induced apoptosis was not correlated to protection.