title: Timing of plasmid cytokine (IL-2/Ig) administration affects HIV-1 vaccine immunogenicity in HIV-seronegative subjects.
abstract: BACKGROUND
  To investigate the potential immunostimulatory effect of interleukin (IL) 2 as a human immunodeficiency virus type 1 (HIV-1) vaccine adjuvant, we conducted a study of a plasmid coding for a fusion protein of IL-2 and immunoglobulin (IL-2/Ig).
  
  
  METHODS
  This phase I trial evaluated an HIV-1 DNA vaccine with the plasmid cytokine adjuvant (IL-2/Ig) in 70 HIV-negative adults. Subjects received placebo (group C), adjuvant alone (group A), vaccine alone (group D), increasing doses of adjuvant concurrent with vaccine (groups T1-T4), or adjuvant given 2 days after vaccine (group T5).
  
  
  RESULTS
  No significant differences in adverse events were observed between treatment groups. Cellular immune responses to envelope protein EnvA peptides were detected by interferon (IFN) γ and IL-2 enzyme-linked immunospot (ELISPOT) assays in 50% and 40% of subjects, respectively, in T4, and in 100% and 80% in T5. The median responses for groups T4 and T5, respectively, were 90 and 193 spot-forming cells (SFCs)/10⁶ peripheral blood mononuclear cells (P = .004; T4 vs T5) for the IL-2 ELISPOT assay and 103 and 380 SFCs/10⁶ PBMCs (P = .003; T4 vs T5) for the IFN-γ ELISPOT assay. A trend to more durable cellular immune responses in T5 was observed at 1 year (T5 vs T4/D; P = .07). Higher anti-Env antibody responses were detected with T5 than with T4.
  
  
  CONCLUSIONS
  Plasmid IL-2/Ig significantly increased immune responses when administered 2 days after the DNA vaccine, compared with simultaneous administration. These observations have important implications for the development of cytokine augmentation strategies.
  
  
  BACKGROUND
  NCT00069030.
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, MA, USA.
authors.forename: Lindsey R
authors.initials: LR
authors.lastname: Baden
authors.forename: William A
authors.initials: WA
authors.lastname: Blattner
authors.forename: Cecilia
authors.initials: C
authors.lastname: Morgan
authors.forename: Yunda
authors.initials: Y
authors.lastname: Huang
authors.forename: Olivier D
authors.initials: OD
authors.lastname: Defawe
authors.forename: Magdalena E
authors.initials: ME
authors.lastname: Sobieszczyk
authors.forename: Nidhi
authors.initials: N
authors.lastname: Kochar
authors.forename: Georgia D
authors.initials: GD
authors.lastname: Tomaras
authors.forename: M Juliana
authors.initials: MJ
authors.lastname: McElrath
authors.forename: Nina
authors.initials: N
authors.lastname: Russell
authors.forename: Kara
authors.initials: K
authors.lastname: Brandariz
authors.forename: Massimo
authors.initials: M
authors.lastname: Cardinali
authors.forename: Barney S
authors.initials: BS
authors.lastname: Graham
authors.forename: Dan H
authors.initials: DH
authors.lastname: Barouch
authors.forename: Raphael
authors.initials: R
authors.lastname: Dolin
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000032:analysis; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D018023:HIV Seronegativity / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000276:immunology; D008297:Male; D010957:Plasmids / Q000008:administration & dosage; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D014759:Viral Envelope Proteins / Q000032:analysis; D055815:Young Adult
chemical_list: D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D007376:Interleukin-2; D019444:Vaccines, DNA; D014759:Viral Envelope Proteins