Gene combination raises broad human immunodeficiency virus-specific cytotoxicity

DNA plasmid immunization has the important advantage over traditional vacci nes of making it possible to combine selected genes into one vaccine. The e fficacy of a combination of DNA plasmids encoding the nef, rev, and tat HIV -1 regulatory genes in inducing cellular immune responses was analyzed in a symptomatic HIV-1-infected patients. Patients initially selected for having low or no detectable immune responses to Nef, Rev, or Tat antigens develop ed MHC class I-restricted cytolytic activities as well as enhanced bystande r effects. The induction of memory cells against target cells infected with the whole HIV-1 genome was analyzed by using a pseudovirus HIV-1/murine le ukemia virus (MuLV), and target cells infected with vaccinia virus carrying the respective gene. The most remarkable change observed after immunizatio n with the gene combination was an increase in cytotoxic T lymphocyte (CTL) precursors to target cells infected with the whole HIV-1 genome. Infection by the pseudotype HIV-1/MuLV virus should result in a multitude of HIV-1 p eptides presented on the target cell surface, representative of the in vivo situation. An in vitro assessment of the expression of the single and comb ined gene products showed that this was consistent with the induction of CT L responses in vivo. No clinical advantage or adverse effects were noted. T herapeutic effects of such immunization may become measurable by structured therapy interruption.