title: Gene combination raises broad human immunodeficiency virus-specific cytotoxicity.
abstract: DNA plasmid immunization has the important advantage over traditional vaccines of making it possible to combine selected genes into one vaccine. The efficacy of a combination of DNA plasmids encoding the nef, rev, and tat HIV-1 regulatory genes in inducing cellular immune responses was analyzed in asymptomatic HIV-1-infected patients. Patients initially selected for having low or no detectable immune responses to Nef, Rev, or Tat antigens developed MHC class I-restricted cytolytic activities as well as enhanced bystander 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 leukemia virus (MuLV), and target cells infected with vaccinia virus carrying the respective gene. The most remarkable change observed after immunization 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 peptides presented on the target cell surface, representative of the in vivo situation. An in vitro assessment of the expression of the single and combined gene products showed that this was consistent with the induction of CTL responses in vivo. No clinical advantage or adverse effects were noted. Therapeutic effects of such immunization may become measurable by structured therapy interruption.
authors.affiliation: Swedish Institute for Infectious Disease Control, Microbiology and Tumor Biology Center, Karolinska Institute, SE-171 82 Solna, Sweden.
authors.forename: S A
authors.initials: SA
authors.lastname: Calarota
authors.forename: A
authors.initials: A
authors.lastname: Kjerrström
authors.forename: K B
authors.initials: KB
authors.lastname: Islam
authors.forename: B
authors.initials: B
authors.lastname: Wahren
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000235:genetics* / Q000276:immunology* / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D018899:CpG Islands / Q000235:genetics; D003602:Cytotoxicity, Immunologic; D015870:Gene Expression; D015693:Gene Products, nef / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use; D015694:Gene Products, rev / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use; D015696:Gene Products, tat / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use; D005814:Genes, Viral / Q000235:genetics; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics; D015488:HIV Antigens / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D015658:HIV Infections / Q000276:immunology* / Q000628:therapy / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology; D006367:HeLa Cells; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D009052:Leukemia Virus, Murine / Q000235:genetics; D008213:Lymphocyte Activation; D010957:Plasmids / Q000235:genetics; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology*; D014611:Vaccination; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics* / Q000276:immunology* / Q000627:therapeutic use; D014616:Vaccinia virus / Q000235:genetics; D054311:nef Gene Products, Human Immunodeficiency Virus; D054321:rev Gene Products, Human Immunodeficiency Virus; D054322:tat Gene Products, Human Immunodeficiency Virus
chemical_list: D016915:AIDS Vaccines; D015693:Gene Products, nef; D015694:Gene Products, rev; D015696:Gene Products, tat; D015488:HIV Antigens; D015395:Histocompatibility Antigens Class I; D019444:Vaccines, DNA; D054311:nef Gene Products, Human Immunodeficiency Virus; D054321:rev Gene Products, Human Immunodeficiency Virus; D054322:tat Gene Products, Human Immunodeficiency Virus