title: Single DermaVir immunization: dose-dependent expansion of precursor/memory T cells against all HIV antigens in HIV-1 infected individuals.
abstract: BACKGROUND
  The GIHU004 study was designed to evaluate the safety and immunogenicity of three doses of DermaVir immunization in HIV-infected subjects on fully suppressive combination antiretroviral therapy (cART).
  
  
  RESULTS
  This first-in-human dose escalation study was conducted with three topical DermaVir doses targeted to epidermal Langerhans cells to express fifteen HIV antigens in draining lymph nodes: 0.1 mg DNA targeted to two, 0.4 mg and 0.8 mg DNA targeted to four lymph nodes. Particularly, in the medium dose cohort 0.1 mg DNA was targeted per draining lymph node via ∼8 million Langerhans cells located in 80 cm(2) epidermis area. The 28-days study with 48-week safety follow-up evaluated HIV-specific T cell responses against Gag p17, Gag p24 and Gag p15, Tat and Rev antigens. DermaVir-associated side effects were mild, transient and not dose-dependent. Boosting of HIV-specific effector CD4(+) and CD8(+) T cells expressing IFN-gamma and IL-2 was detected against several antigens in every subject of the medium dose cohort. The striking result was the dose-dependent expansion of HIV-specific precursor/memory T cells with high proliferation capacity. In low, medium and high dose cohorts this HIV-specific T cell population increased by 325-, 136,202 and 50,759 counts after 4 weeks, and by 3,899, 9,878 and 18,382 counts after one year, respectively, compared to baseline.
  
  
  CONCLUSIONS
  Single immunization with the DermaVir candidate therapeutic vaccine was safe and immunogenic in HIV-infected individuals. Based on the potent induction of Gag, Tat and Rev-specific memory T cells, especially in the medium dose cohort, we speculate that DermaVir boost T cell responses specific to all the 15 HIV antigens expressed from the single DNA. For durable immune reactivity repeated DermaVir immunization might be required since the frequency of DermaVir-boosted HIV-specific memory T cells decreased during the 48-week follow up.
  
  
  BACKGROUND
  ClinicalTrial.gov NCT00712530.
authors.affiliation: Genetic Immunity, Budapest, Hungary and Genetic Immunity Inc, Mclean, Virginia, United States of America. lisziewj@geneticimmunity.com
authors.forename: Julianna
authors.initials: J
authors.lastname: Lisziewicz
authors.forename: Nyasha
authors.initials: N
authors.lastname: Bakare
authors.forename: Sandra A
authors.initials: SA
authors.lastname: Calarota
authors.forename: Dénes
authors.initials: D
authors.lastname: Bánhegyi
authors.forename: János
authors.initials: J
authors.lastname: Szlávik
authors.forename: Eszter
authors.initials: E
authors.lastname: Ujhelyi
authors.forename: Enikő R
authors.initials: ER
authors.lastname: Tőke
authors.forename: Levente
authors.initials: L
authors.lastname: Molnár
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Lisziewicz
authors.forename: Brigitte
authors.initials: B
authors.lastname: Autran
authors.forename: Franco
authors.initials: F
authors.lastname: Lori
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage* / Q000276:immunology; D000293:Adolescent; D000328:Adult; D000956:Antigens, Viral / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015331:Cohort Studies; D004306:Dose-Response Relationship, Immunologic; D004817:Epidermis / Q000276:immunology; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000276:immunology* / Q000628:therapy; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000276:immunology; D007801:Langerhans Cells / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D008297:Male; D008875:Middle Aged
chemical_list: D016915:AIDS Vaccines; D000956:Antigens, Viral; C501366:DermaVir; D007371:Interferon-gamma