title: DNA vaccine delivered by a needle-free injection device improves potency of priming for antibody and CD8+ T-cell responses after rAd5 boost in a randomized clinical trial.
abstract: BACKGROUND
  DNA vaccine immunogenicity has been limited by inefficient delivery. Needle-free delivery of DNA using a CO2-powered Biojector® device was compared to delivery by needle and syringe and evaluated for safety and immunogenicity.
  
  
  METHODS
  Forty adults, 18-50 years, were randomly assigned to intramuscular (IM) vaccinations with DNA vaccine, VRC-HIVDNA016-00-VP, (weeks 0, 4, 8) by Biojector® 2000™ or needle and syringe (N/S) and boosted IM at week 24 with VRC-HIVADV014-00-VP (rAd5) with N/S at 10(10) or 10(11) particle units (PU). Equal numbers per assigned schedule had low (≤500) or high (>500) reciprocal titers of preexisting Ad5 neutralizing antibody.
  
  
  RESULTS
  120 DNA and 39 rAd5 injections were given; 36 subjects completed follow-up research sample collections. IFN-γ ELISpot response rates were 17/19 (89%) for Biojector® and 13/17 (76%) for N/S delivery at Week 28 (4 weeks post rAd5 boost). The magnitude of ELISpot response was about 3-fold higher in Biojector® compared to N/S groups. Similar effects on response rates and magnitude were observed for CD8+, but not CD4+ T-cell responses by ICS. Env-specific antibody responses were about 10-fold higher in Biojector-primed subjects.
  
  
  CONCLUSIONS
  DNA vaccination by Biojector® was well-tolerated and compared to needle injection, primed for greater IFN-γ ELISpot, CD8+ T-cell, and antibody responses after rAd5 boosting.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00109629.
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. bgraham@nih.gov
authors.forename: Barney S
authors.initials: BS
authors.lastname: Graham
authors.forename: Mary E
authors.initials: ME
authors.lastname: Enama
authors.forename: Martha C
authors.initials: MC
authors.lastname: Nason
authors.forename: Ingelise J
authors.initials: IJ
authors.lastname: Gordon
authors.forename: Sheila A
authors.initials: SA
authors.lastname: Peel
authors.forename: Julie E
authors.initials: JE
authors.lastname: Ledgerwood
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Plummer
authors.forename: John R
authors.initials: JR
authors.lastname: Mascola
authors.forename: Robert T
authors.initials: RT
authors.lastname: Bailer
authors.forename: Mario
authors.initials: M
authors.lastname: Roederer
authors.forename: Richard A
authors.initials: RA
authors.lastname: Koup
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Nabel
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004274:DNA, Recombinant / Q000235:genetics; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D015497:HIV-1 / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D056724:Immunity, Humoral / Q000276:immunology; D007117:Immunization, Secondary / Q000379:methods*; D007267:Injections; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000378:metabolism; D012449:Safety; D014611:Vaccination / Q000295:instrumentation*; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000009:adverse effects / Q000235:genetics / Q000276:immunology*; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D004274:DNA, Recombinant; D010446:Peptide Fragments; D019444:Vaccines, DNA