title: Safety and immunogenicity of an HIV-1 gag DNA vaccine with or without IL-12 and/or IL-15 plasmid cytokine adjuvant in healthy, HIV-1 uninfected adults.
abstract: BACKGROUND
  DNA vaccines are a promising approach to vaccination since they circumvent the problem of vector-induced immunity. DNA plasmid cytokine adjuvants have been shown to augment immune responses in small animals and in macaques.
  
  
  RESULTS
  We performed two first in human HIV vaccine trials in the US, Brazil and Thailand of an RNA-optimized truncated HIV-1 gag gene (p37) DNA derived from strain HXB2 administered either alone or in combination with dose-escalation of IL-12 or IL-15 plasmid cytokine adjuvants. Vaccinations with both the HIV immunogen and cytokine adjuvant were generally well-tolerated and no significant vaccine-related adverse events were identified. A small number of subjects developed asymptomatic low titer antibodies to IL-12 or IL-15. Cellular immunogenicity following 3 and 4 vaccinations was poor, with response rates to gag of 4.9%/8.7% among vaccinees receiving gag DNA alone, 0%/11.5% among those receiving gag DNA+IL-15, and no responders among those receiving DNA+high dose (1500 ug) IL-12 DNA. However, after three doses, 44.4% (4/9) of vaccinees receiving gag DNA and intermediate dose (500 ug) of IL-12 DNA demonstrated a detectable cellular immune response.
  
  
  CONCLUSIONS
  This combination of HIV gag DNA with plasmid cytokine adjuvants was well tolerated. There were minimal responses to HIV gag DNA alone, and no apparent augmentation with either IL-12 or IL-15 plasmid cytokine adjuvants. Despite the promise of DNA vaccines, newer formulations or methods of delivery will be required to increase their immunogenicity.
  
  
  BACKGROUND
  Clinicaltrials.gov NCT00115960 NCT00111605.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Department of Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, United States of Ameica. s.kalams@vanderbilt.edu
authors.forename: Spyros A
authors.initials: SA
authors.lastname: Kalams
authors.forename: Scott
authors.initials: S
authors.lastname: Parker
authors.forename: Xia
authors.initials: X
authors.lastname: Jin
authors.forename: Marnie
authors.initials: M
authors.lastname: Elizaga
authors.forename: Barbara
authors.initials: B
authors.lastname: Metch
authors.forename: Maggie
authors.initials: M
authors.lastname: Wang
authors.forename: John
authors.initials: J
authors.lastname: Hural
authors.forename: Michael
authors.initials: M
authors.lastname: Lubeck
authors.forename: John
authors.initials: J
authors.lastname: Eldridge
authors.forename: Massimo
authors.initials: M
authors.lastname: Cardinali
authors.forename: William A
authors.initials: WA
authors.lastname: Blattner
authors.forename: Magda
authors.initials: M
authors.lastname: Sobieszczyk
authors.forename: Vinai
authors.initials: V
authors.lastname: Suriyanon
authors.forename: Artur
authors.initials: A
authors.lastname: Kalichman
authors.forename: David B
authors.initials: DB
authors.lastname: Weiner
authors.forename: Lindsey R
authors.initials: LR
authors.lastname: Baden
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology; D000276:Adjuvants, Immunologic; D000293:Adolescent; D000328:Adult; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006262:Health; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology*; D019409:Interleukin-15 / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010957:Plasmids / Q000276:immunology; D014611:Vaccination; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology; D055815:Young Adult; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D019409:Interleukin-15; D019444:Vaccines, DNA; D054301:gag Gene Products, Human Immunodeficiency Virus; D018664:Interleukin-12; D007371:Interferon-gamma