title: Broad immunogenicity of a multigene, multiclade HIV-1 DNA vaccine boosted with heterologous HIV-1 recombinant modified vaccinia virus Ankara.
abstract: BACKGROUND
  A human immunodeficiency virus (HIV) vaccine that limits disease and transmission is urgently needed. This clinical trial evaluated the safety and immunogenicity of an HIV vaccine that combines a plasmid-DNA priming vaccine and a modified vaccinia virus Ankara (MVA) boosting vaccine.
  
  
  METHODS
  Forty healthy volunteers were injected with DNA plasmids containing gp160 of HIV-1 subtypes A, B, and C; rev B; p17/p24 gag A and B, and RTmut B by use of a needle-free injection system. The vaccine was administered intradermally or intramuscularly, with or without recombinant granulocyte macrophage colony-stimulating factor, and boosted with a heterologous MVA containing env, gag, and pol of CRF01A_E. Immune responses were monitored with HIV-specific interferon (IFN)-gamma and interleukin (IL)-2 ELISpot and lymphoproliferative assays (LPAs).
  
  
  RESULTS
  Vaccine-related adverse events were mild and tolerable. After receipt of the DNA priming vaccine, 11 (30%) of 37 vaccinees had HIV-specific IFN-gamma responses. After receipt of the MVA boosting vaccine, ELISpot assays showed that 34 (92%) of 37 vaccinees had HIV-specific IFN-gamma responses, 32 (86%) to Gag and 24 (65%) to Env. IFN-gamma production was detected in both the CD8(+) T cell compartment (5 of 9 selected vaccinees) and the CD4(+) T cell compartment (9 of 9). ELISpot results showed that 25 (68%) of 37 vaccinees had a positive IL-2 response and 35 (92%) of 38 had a positive LPA response. Of 38 subjects, a total of 37 (97%) were responders. One milligram of HIV-1 DNA administered intradermally was as effective as 4 mg administered intramuscularly in priming for the MVA boosting vaccine.
  
  
  CONCLUSIONS
  This HIV-DNA priming-MVA boosting approach is safe and highly immunogenic.
  
  
  BACKGROUND
  International Standard Randomised Controlled Trial number: ISRCTN32604572 .
authors.affiliation: Department of Clinical Science and Education, Södersjukhuset, Sweden. Eric.sandstrom@sodersjukhuset.se
authors.forename: Eric
authors.initials: E
authors.lastname: Sandström
authors.forename: Charlotta
authors.initials: C
authors.lastname: Nilsson
authors.forename: Bo
authors.initials: B
authors.lastname: Hejdeman
authors.forename: Andreas
authors.initials: A
authors.lastname: Bråve
authors.forename: Göran
authors.initials: G
authors.lastname: Bratt
authors.forename: Merlin
authors.initials: M
authors.lastname: Robb
authors.forename: Josephine
authors.initials: J
authors.lastname: Cox
authors.forename: Thomas
authors.initials: T
authors.lastname: Vancott
authors.forename: Mary
authors.initials: M
authors.lastname: Marovich
authors.forename: Richard
authors.initials: R
authors.lastname: Stout
authors.forename: Said
authors.initials: S
authors.lastname: Aboud
authors.forename: Muhammad
authors.initials: M
authors.lastname: Bakari
authors.forename: Kisali
authors.initials: K
authors.lastname: Pallangyo
authors.forename: Karl
authors.initials: K
authors.lastname: Ljungberg
authors.forename: Bernard
authors.initials: B
authors.lastname: Moss
authors.forename: Patricia
authors.initials: P
authors.lastname: Earl
authors.forename: Nelson
authors.initials: N
authors.lastname: Michael
authors.forename: Deborah
authors.initials: D
authors.lastname: Birx
authors.forename: Fred
authors.initials: F
authors.lastname: Mhalu
authors.forename: Britta
authors.initials: B
authors.lastname: Wahren
authors.forename: Gunnel
authors.initials: G
authors.lastname: Biberfeld
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology* / Q000592:standards*; D000328:Adult; D000917:Antibody Formation / Q000276:immunology; D005260:Female; D005822:Genetic Vectors / Q000235:genetics / Q000276:immunology; D015658:HIV Infections / Q000517:prevention & control*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology; D019444:Vaccines, DNA / Q000009:adverse effects / Q000235:genetics / Q000276:immunology* / Q000592:standards*; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology*; D055815:Young Adult
chemical_list: D016915:AIDS Vaccines; D019444:Vaccines, DNA