title: Phase 1 safety and immunogenicity evaluation of a multiclade HIV-1 DNA candidate vaccine.
abstract: BACKGROUND
  Gene-based vaccine delivery is an important strategy in the development of a preventive vaccine for acquired immunodeficiency syndrome (AIDS). Vaccine Research Center (VRC) 004 is the first phase 1 dose-escalation study of a multiclade HIV-1 DNA vaccine.
  
  
  METHODS
  VRC-HIVDNA009-00-VP is a 4-plasmid mixture encoding subtype B Gag-Pol-Nef fusion protein and modified envelope (Env) constructs from subtypes A, B, and C. Fifty healthy, uninfected adults were randomized to receive either placebo (n=10) or study vaccine at 2 mg (n=5), 4 mg (n=20), or 8 mg (n=15) by needle-free intramuscular injection. Humoral responses (measured by enzyme-linked immunosorbant assay, Western blotting, and neutralization assay) and T cell responses (measured by enzyme-linked immunospot assay and intracellular cytokine staining after stimulation with antigen-specific peptide pools) were measured.
  
  
  RESULTS
  The vaccine was well tolerated and induced cellular and humoral responses. The maximal CD4(+) and CD8(+) T cell responses occurred after 3 injections and were in response to Env peptide pools. The pattern of cytokine expression by vaccine-induced HIV-specific T cells evolved over time, with a diminished frequency of interferon- gamma -producing T cells and an increased frequency of interleukin-2-producing T cells at 1 year.
  
  
  CONCLUSIONS
  DNA vaccination induced antibody to and T cell responses against 3 major HIV-1 subtypes and will be further evaluated as a potential component of a preventive AIDS vaccine regimen.
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-3017, USA. bgraham@mail.nih.gov
authors.forename: Barney S
authors.initials: BS
authors.lastname: Graham
authors.forename: Richard A
authors.initials: RA
authors.lastname: Koup
authors.forename: Mario
authors.initials: M
authors.lastname: Roederer
authors.forename: Robert T
authors.initials: RT
authors.lastname: Bailer
authors.forename: Mary E
authors.initials: ME
authors.lastname: Enama
authors.forename: Zoe
authors.initials: Z
authors.lastname: Moodie
authors.forename: Julie E
authors.initials: JE
authors.lastname: Martin
authors.forename: Margaret M
authors.initials: MM
authors.lastname: McCluskey
authors.forename: Bimal K
authors.initials: BK
authors.lastname: Chakrabarti
authors.forename: Laurie
authors.initials: L
authors.lastname: Lamoreaux
authors.forename: Charla A
authors.initials: CA
authors.lastname: Andrews
authors.forename: Phillip L
authors.initials: PL
authors.lastname: Gomez
authors.forename: John R
authors.initials: JR
authors.lastname: Mascola
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Nabel
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D000918:Antibody Specificity; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000032:analysis / Q000096:biosynthesis; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015685:Fusion Proteins, gag-pol / Q000235:genetics / Q000276:immunology; D015693:Gene Products, nef / Q000235:genetics / Q000276:immunology; D005822:Genetic Vectors; D015658:HIV Infections / Q000097:blood / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007115:Immunization Schedule; D007273:Injections, Intramuscular; D008297:Male; D009500:Neutralization Tests; D010957:Plasmids; D014611:Vaccination; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology; D054311:nef Gene Products, Human Immunodeficiency Virus
chemical_list: D016915:AIDS Vaccines; D000914:Antibodies, Viral; D016207:Cytokines; D015685:Fusion Proteins, gag-pol; D015693:Gene Products, nef; D019444:Vaccines, DNA; D014759:Viral Envelope Proteins; D054311:nef Gene Products, Human Immunodeficiency Virus