Evaluation of a lipopeptide immunogen as a therapeutic in HIV type 1-seropositive individuals

A 32-amino acid HIV-1 Gag immunogen was assessed for its ability to augment existing virus-specific CTL responses in chronically HIV-1-infected indivi duals. The immunogen was an HIV-1 synthetic lipopeptide conjugate composed of an N-palmitoyl-S-[2,3-bis(palmitoyloxy)-(2R)-propyl-N-(R)-cysteinyl] gro up covalently coupled to a synthetic 32-amino acid Gag peptide containing a t least 5 CTL epitopes known to be restricted by HLA-A33, -B8, -B27, -B35, and -Bw62. This potential immunotherapeutic was first determined to be safe in six HIV-1-seropositive subjects, with no adverse clinical effects noted during a 182-day period after administration of a dose of 350 mu g. The im munogenicity of this lipopeptide conjugate was then assessed in a pilot stu dy in nine HIV-1-seropositive volunteers with peripheral blood CD4(+) lymph ocyte counts of >500/mu l, Three groups of individuals were studied: HLA-se lected subjects who received 350 mu g of the immunogen on days 0, 28, and 5 6 (four subjects); HLA-selected subjects who received a placebo according t o a similar inoculation schedule (three subjects); and HLA-mismatched subje cts who received the experimental immunogen (two subjects). All subjects we re monitored for 26 weeks. After treatment, PBLs from two of the four HLA-s elected subjects who received the experimental immunogen showed a transient increase in Gag peptide-specific bulk CTL activity. None of the placebo-va ccinated or vaccinated HLA-mismatched subjects showed any change in bulk Ga g peptide-specific CTL activity. However, no consistent decrease in plasma HIV-1 RNA levels was noted in any of the subjects. The present study illust rates that this peptide formulation may not be a sufficiently potent immuno gen to significantly augment HIV-1-specific CTLs and to decrease virus load in HIV-1-seropositive individuals.