title: HIV-DNA Given with or without Intradermal Electroporation Is Safe and Highly Immunogenic in Healthy Swedish HIV-1 DNA/MVA Vaccinees: A Phase I Randomized Trial.
abstract: BACKGROUND
  We compared safety and immunogenicity of intradermal (ID) vaccination with and without electroporation (EP) in a phase I randomized placebo-controlled trial of an HIV-DNA prime HIV-MVA boost vaccine in healthy Swedish volunteers.
  
  
  METHODS
  HIV-DNA plasmids encoding HIV-1 genes gp160 subtypes A, B and C; Rev B; Gag A and B and RTmut B were given ID at weeks 0, 6 and 12 in a dose of 0.6 mg. Twenty-five volunteers received vaccine using a needle-free device (ZetaJet) with (n=16) or without (n=9) ID EP (Dermavax). Five volunteers were placebo recipients. Boosting with recombinant MVA-CMDR expressing HIV-1 Env, Gag, Pol of CRF01_AE (HIV-MVA) or placebo was performed at weeks 24 and 40. Nine of the vaccinees received a subtype C CN54 gp140 protein boost together with HIV-MVA.
  
  
  RESULTS
  The ID/EP delivery was very well tolerated. After three HIV-DNA immunizations, no statistically significant difference was seen in the IFN-γ ELISpot response rate to Gag between HIV-DNA ID/EP recipients (5/15, 33%) and HIV-DNA ID recipients (1/7, 14%, p=0.6158). The first HIV-MVA or HIV-MVA+gp140 vaccination increased the IFN-γ ELISpot response rate to 18/19 (95%). CD4+ and/or CD8+ T cell responses to Gag or Env were demonstrable in 94% of vaccinees. A balanced CD4+ and CD8+ T cell response was noted, with 78% and 71% responders, respectively. IFN-γ and IL-2 dominated the CD4+ T cell response to Gag and Env. The CD8+ response to Gag was broader with expression of IFN-γ, IL-2, MIP-1β and/or CD107. No differences were seen between DNA vaccine groups. Binding antibodies were induced after the second HIV-MVA+/-gp140 in 93% of vaccinees to subtype C Env, with the highest titers among EP/gp140 recipients.
  
  
  CONCLUSIONS
  Intradermal electroporation of HIV-DNA was well tolerated. Strong cell- and antibody-mediated immune responses were elicited by the HIV-DNA prime and HIV-MVA boosting regimen, with or without intradermal electroporation use.
  
  
  BACKGROUND
  International Standard Randomised Controlled Trial Number (ISRCTN) 60284968.
authors.affiliation: Department of Microbiology, Public Health Agency of Sweden, Solna, Sweden; Department of Microbiology, Tumor and Cell biology, Karolinska Institutet, Stockholm, Sweden; Department of Laboratory Medicine, Karolinska Institutet, Huddinge, Sweden.
authors.forename: Charlotta
authors.initials: C
authors.lastname: Nilsson
authors.affiliation: Venhälsan, Department of Education and Clinical Research, Karolinska Institutet, Södersjukhuset, Stockholm, Sweden.
authors.forename: Bo
authors.initials: B
authors.lastname: Hejdeman
authors.affiliation: Department of Microbiology, Public Health Agency of Sweden, Solna, Sweden.
authors.forename: Karina
authors.initials: K
authors.lastname: Godoy-Ramirez
authors.affiliation: Department of Microbiology, Public Health Agency of Sweden, Solna, Sweden.
authors.forename: Teghesti
authors.initials: T
authors.lastname: Tecleab
authors.affiliation: Viral Evolution and Transmission Unit, Division of Immunology, Transplantation and infectious diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Scarlatti
authors.affiliation: Department of Microbiology, Public Health Agency of Sweden, Solna, Sweden.
authors.forename: Andreas
authors.initials: A
authors.lastname: Bråve
authors.affiliation: National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda MD, United States of America.
authors.forename: Patricia L
authors.initials: PL
authors.lastname: Earl
authors.affiliation: Bioject Inc., Tigard, Oregon, United States of America.
authors.forename: Richard R
authors.initials: RR
authors.lastname: Stout
authors.affiliation: Military HIV Research Program, Walter Reed Army Institute of Research, Rockville, Maryland, United States of America.
authors.forename: Merlin L
authors.initials: ML
authors.lastname: Robb
authors.affiliation: Imperial College London, Department of Infectious Diseases, Division of Medicine, Norfolk Place, London, United Kingdom.
authors.forename: Robin J
authors.initials: RJ
authors.lastname: Shattock
authors.affiliation: Department of Microbiology, Public Health Agency of Sweden, Solna, Sweden; Department of Microbiology, Tumor and Cell biology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Gunnel
authors.initials: G
authors.lastname: Biberfeld
authors.affiliation: Venhälsan, Department of Education and Clinical Research, Karolinska Institutet, Södersjukhuset, Stockholm, Sweden.
authors.forename: Eric
authors.initials: E
authors.lastname: Sandström
authors.affiliation: Department of Microbiology, Tumor and Cell biology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Britta
authors.initials: B
authors.lastname: Wahren
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage* / Q000009:adverse effects; D000328:Adult; D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology; D000920:Antibody-Dependent Cell Cytotoxicity; D018274:Electroporation; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D015483:HIV Antibodies / Q000097:blood / Q000276:immunology; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology*; D064368:Healthy Volunteers; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D056724:Immunity, Humoral / Q000276:immunology; D007271:Injections, Intradermal; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D013548:Sweden; D014611:Vaccination; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000009:adverse effects; D055815:Young Adult
chemical_list: D016915:AIDS Vaccines; D057134:Antibodies, Neutralizing; D015483:HIV Antibodies; D019444:Vaccines, DNA; D007371:Interferon-gamma