title: A phase IIA randomized clinical trial of a multiclade HIV-1 DNA prime followed by a multiclade rAd5 HIV-1 vaccine boost in healthy adults (HVTN204).
abstract: BACKGROUND
  The safety and immunogenicity of a vaccine regimen consisting of a 6-plasmid HIV-1 DNA prime (envA, envB, envC, gagB, polB, nefB) boosted by a recombinant adenovirus serotype-5 (rAd5) HIV-1 with matching inserts was evaluated in HIV-seronegative participants from South Africa, United States, Latin America and the Caribbean.
  
  
  METHODS
  480 participants were evenly randomized to receive either: DNA (4 mg i.m. by Biojector) at 0, 1 and 2 months, followed by rAd5 (10(10) PU i.m. by needle/syringe) at 6 months; or placebo. Participants were monitored for reactogenicity and adverse events throughout the 12-month study. Peak and duration of HIV-specific humoral and cellular immune responses were evaluated after the prime and boost.
  
  
  RESULTS
  The vaccine was well tolerated and safe. T-cell responses, detected by interferon-γ (IFN-γ) ELISpot to global potential T-cell epitopes (PTEs) were observed in 70.8% (136/192) of vaccine recipients overall, most frequently to Gag (54.7%) and to Env (54.2%). In U.S. vaccine recipients T-cell responses were less frequent in Ad5 sero-positive versus sero-negative vaccine recipients (62.5% versus 85.7% respectively, p = 0.035). The frequency of HIV-specific CD4+ and CD8+ T-cell responses detected by intracellular cytokine staining were similar (41.8% and 47.2% respectively) and most secreted ≥2 cytokines. The vaccine induced a high frequency (83.7%-94.6%) of binding antibody responses to consensus Group M, and Clades A, B and C gp140 Env oligomers. Antibody responses to Gag were elicited in 46% of vaccine recipients.
  
  
  CONCLUSIONS
  The vaccine regimen was well-tolerated and induced polyfunctional CD4+ and CD8+ T-cells and multi-clade anti-Env binding antibodies.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00125970.
authors.affiliation: Aurum Institute for Health Research, Klerksdorp, South Africa.
authors.forename: Gavin J
authors.initials: GJ
authors.lastname: Churchyard
authors.forename: Cecilia
authors.initials: C
authors.lastname: Morgan
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Adams
authors.forename: John
authors.initials: J
authors.lastname: Hural
authors.forename: Barney S
authors.initials: BS
authors.lastname: Graham
authors.forename: Zoe
authors.initials: Z
authors.lastname: Moodie
authors.forename: Doug
authors.initials: D
authors.lastname: Grove
authors.forename: Glenda
authors.initials: G
authors.lastname: Gray
authors.forename: Linda-Gail
authors.initials: LG
authors.lastname: Bekker
authors.forename: M Juliana
authors.initials: MJ
authors.lastname: McElrath
authors.forename: Georgia D
authors.initials: GD
authors.lastname: Tomaras
authors.forename: Paul
authors.initials: P
authors.lastname: Goepfert
authors.forename: Spyros
authors.initials: S
authors.lastname: Kalams
authors.forename: Lindsey R
authors.initials: LR
authors.lastname: Baden
authors.forename: Michelle
authors.initials: M
authors.lastname: Lally
authors.forename: Raphael
authors.initials: R
authors.lastname: Dolin
authors.forename: William
authors.initials: W
authors.lastname: Blattner
authors.forename: Artur
authors.initials: A
authors.lastname: Kalichman
authors.forename: J Peter
authors.initials: JP
authors.lastname: Figueroa
authors.forename: Jean
authors.initials: J
authors.lastname: Pape
authors.forename: Mauro
authors.initials: M
authors.lastname: Schechter
authors.forename: Olivier
authors.initials: O
authors.lastname: Defawe
authors.forename: Stephen C
authors.initials: SC
authors.lastname: De Rosa
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Nabel
authors.forename: Lawrence
authors.initials: L
authors.lastname: Corey
authors.forename: Michael C
authors.initials: MC
authors.lastname: Keefer
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D000256:Adenoviridae / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000740:Anemia / Q000139:chemically induced; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D054298:Human Immunodeficiency Virus Proteins / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007114:Immunization / Q000009:adverse effects / Q000379:methods; D007117:Immunization, Secondary / Q000009:adverse effects / Q000379:methods; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007371:Interferon-gamma / Q000097:blood / Q000276:immunology; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*; D055815:Young Adult; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology; D054302:pol Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D000914:Antibodies, Viral; D054298:Human Immunodeficiency Virus Proteins; D007074:Immunoglobulin G; D019444:Vaccines, DNA; D054299:env Gene Products, Human Immunodeficiency Virus; D054301:gag Gene Products, Human Immunodeficiency Virus; D054311:nef Gene Products, Human Immunodeficiency Virus; C514837:nef protein, Human immunodeficiency virus 1; D054302:pol Gene Products, Human Immunodeficiency Virus; D007371:Interferon-gamma