title: Phase I randomized clinical trial of VRC DNA and rAd5 HIV-1 vaccine delivery by intramuscular (i.m.), subcutaneous (s.c.) and intradermal (i.d.) administration (VRC 011).
abstract: BACKGROUND
  Phase 1 evaluation of the VRC HIV DNA and rAd5 vaccines delivered intramuscularly (i.m.) supported proceeding to a Phase 2 b efficacy study. Here we report comparison of the i.m., subcutaneous (s.c.) and intradermal (i.d.) routes of administration.
  
  
  METHODS
  Sixty subjects were randomized to 6 schedules to evaluate the i.m., s.c. or i.d. route for prime injections. Three schedules included DNA primes (Wks 0,4,8) and 3 schedules included rAd5 prime (Wk0); all included rAd5 i.m. boost (Wk24). DNA vaccine dosage was 4 mg i.m. or s.c., but 0.4 mg i.d., while all rAd5 vaccinations were 1010 PU. All injections were administered by needle and syringe.
  
  
  RESULTS
  Overall, 27/30 subjects completed 3 DNA primes; 30/30 subjects completed rAd5 primes. Mild local pruritus (itchiness), superficial skin lesions and injection site nodules were associated with i.d. and s.c., but not i.m. injections. All routes induced T-cell and antibody immune responses after rAd5 boosting. Overall, >95% had Env antibody and >80% had Env T-cell responses.
  
  
  CONCLUSIONS
  The pattern of local reactogenicity following i.d. and s.c. injections differed from i.m. injections but all routes were well-tolerated. There was no evidence of an immunogenicity advantage following s.c. or i.d. delivery, supporting i.m. delivery as the preferred route of administration.
  
  
  BACKGROUND
  Clinicaltrials.gov NCT00321061.
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Mary E
authors.initials: ME
authors.lastname: Enama
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Julie E
authors.initials: JE
authors.lastname: Ledgerwood
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Laura
authors.initials: L
authors.lastname: Novik
authors.affiliation: Biostatistics Research Branch, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Martha C
authors.initials: MC
authors.lastname: Nason
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Ingelise J
authors.initials: IJ
authors.lastname: Gordon
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: LaSonji
authors.initials: L
authors.lastname: Holman
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Robert T
authors.initials: RT
authors.lastname: Bailer
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Mario
authors.initials: M
authors.lastname: Roederer
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Koup
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: John R
authors.initials: JR
authors.lastname: Mascola
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Nabel
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Barney S
authors.initials: BS
authors.lastname: Graham
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000235:genetics / Q000276:immunology*; D000256:Adenoviridae / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000276:immunology; D004274:DNA, Recombinant / Q000235:genetics*; D005260:Female; D006801:Humans; D007271:Injections, Intradermal; D007273:Injections, Intramuscular; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D012449:Safety; D013601:T-Lymphocytes / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000009:adverse effects / Q000235:genetics / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D000914:Antibodies, Viral; D004274:DNA, Recombinant; D019444:Vaccines, DNA