title: Comparative cell-mediated immunogenicity of DNA/DNA, DNA/adenovirus type 5 (Ad5), or Ad5/Ad5 HIV-1 clade B gag vaccine prime-boost regimens.
abstract: BACKGROUND
  We report composite results from the Merck phase I program of near-consensus clade B human immunodeficiency virus (HIV) type 1 gag vaccines.
  
  
  METHODS
  Healthy HIV-uninfected adults were enrolled in 6 blinded placebo-controlled studies evaluating the immunogenicity of (1) a 4-dose regimen of a DNA vaccine, (2) a 3-dose priming regimen of the DNA vaccine with a booster dose of an adenovirus type 5 (Ad5)-vectored vaccine, or (3) a 3-dose regimen of the Ad5 vaccine. The DNA plasmid was provided with or without an aluminum phosphate or CRL1005 adjuvant. The primary end point was the unfractionated HIV-1 gag-specific interferon gamma enzyme-linked immunospot (ELISpot) response 4 weeks after the final dose.
  
  
  RESULTS
  Overall, 254 (83%) of 307 subjects randomized to the vaccine groups were evaluable. Adjuvants did not enhance immunogenicity of the DNA vaccine. Postboost ELISpot responder frequencies were higher for Ad5-containing regimens than for the DNA/DNA regimen (33%) but were similar for DNA/Ad5 (55%) and Ad5/Ad5 (50%). DNA/DNA elicited mainly a CD4 response, whereas Ad5/Ad5 elicited mainly a CD8 response; DNA/Ad5 generated CD4 and CD8 responses comparable to those of DNA/DNA and Ad5/Ad5, respectively.
  
  
  CONCLUSIONS
  The DNA vaccine alone or as a priming regimen for the Ad5 vaccine did not increase unfractionated ELISpot responses compared with the Ad5 vaccine alone. Qualitative T cell responses to different vaccine regimens deserve further study.
authors.affiliation: Division of Infectious Disease, Department of Internal Medicine, University of California at Davis, Sacramento, CA 95618, USA. david.asmuth@ucdmc.ucdavis.edu
authors.forename: David M
authors.initials: DM
authors.lastname: Asmuth
authors.forename: Elizabeth L
authors.initials: EL
authors.lastname: Brown
authors.forename: Mark J
authors.initials: MJ
authors.lastname: DiNubile
authors.forename: Xiao
authors.initials: X
authors.lastname: Sun
authors.forename: Carlos
authors.initials: C
authors.lastname: del Rio
authors.forename: Clayton
authors.initials: C
authors.lastname: Harro
authors.forename: Michael C
authors.initials: MC
authors.lastname: Keefer
authors.forename: James G
authors.initials: JG
authors.lastname: Kublin
authors.forename: Sheri A
authors.initials: SA
authors.lastname: Dubey
authors.forename: Lisa S
authors.initials: LS
authors.lastname: Kierstead
authors.forename: Danilo R
authors.initials: DR
authors.lastname: Casimiro
authors.forename: John W
authors.initials: JW
authors.lastname: Shiver
authors.forename: Michael N
authors.initials: MN
authors.lastname: Robertson
authors.forename: Erin K
authors.initials: EK
authors.lastname: Quirk
authors.forename: Devan V
authors.initials: DV
authors.lastname: Mehrotra
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000256:Adenoviridae / Q000276:immunology; D000276:Adjuvants, Immunologic; D000328:Adult; D004279:DNA, Viral / Q000276:immunology*; D005260:Female; D015750:Genes, gag / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007117:Immunization, Secondary / Q000379:methods*; D008297:Male; D008875:Middle Aged; D010919:Placebos; D055815:Young Adult
chemical_list: D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D004279:DNA, Viral; D010919:Placebos