title: Safety and immunogenicity of an HIV adenoviral vector boost after DNA plasmid vaccine prime by route of administration: a randomized clinical trial.
abstract: BACKGROUND
  In the development of HIV vaccines, improving immunogenicity while maintaining safety is critical. Route of administration can be an important factor.
  
  
  RESULTS
  This multicenter, open-label, randomized trial, HVTN 069, compared routes of administration on safety and immunogenicity of a DNA vaccine prime given intramuscularly at 0, 1 and 2 months and a recombinant replication-defective adenovirus type 5 (rAd5) vaccine boost given at 6 months by intramuscular (IM), intradermal (ID), or subcutaneous (SC) route. Randomization was computer-generated by a central data management center; participants and staff were not blinded to group assignment. The outcomes were vaccine reactogenicity and humoral and cellular immunogenicity. Ninety healthy, HIV-1 uninfected adults in the US and Peru, aged 18-50 were enrolled and randomized. Due to the results of the Step Study, injections with rAd5 vaccine were halted; thus 61 received the booster dose of rAd5 vaccine (IM: 20; ID:21; SC:20). After the rAd5 boost, significant differences by study arm were found in severity of headache, pain and erythema/induration. Immune responses (binding and neutralizing antibodies, IFN-γ ELISpot HIV-specific responses and CD4+ and CD8+ T-cell responses by ICS) at four weeks after the rAd5 booster were not significantly different by administration route of the rAd5 vaccine boost (Binding antibody responses: IM: 66.7%; ID: 70.0%; SC: 77.8%; neutralizing antibody responses: IM: 11.1%; ID: 0.0%; SC 16.7%; ELISpot responses: IM: 46.7%; ID: 35.3%; SC: 44.4%; CD4+ T-cell responses: IM: 29.4%; ID: 20.0%; SC: 35.3%; CD8+ T-cell responses: IM: 29.4%; ID: 16.7%; SC: 50.0%.)
  
  
  CONCLUSIONS
  This study was limited by the reduced sample size. The higher frequency of local reactions after ID and SC administration and the lack of sufficient evidence to show that there were any differences in immunogenicity by route of administration do not support changing route of administration for the rAd5 boost.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00384787.
authors.affiliation: Laboratory of Infectious Disease Prevention, New York Blood Center, New York, New York, United States of America. bkoblin@nybloodcenter.org
authors.forename: Beryl A
authors.initials: BA
authors.lastname: Koblin
authors.forename: Martin
authors.initials: M
authors.lastname: Casapia
authors.forename: Cecilia
authors.initials: C
authors.lastname: Morgan
authors.forename: Li
authors.initials: L
authors.lastname: Qin
authors.forename: Zhixue Maggie
authors.initials: ZM
authors.lastname: Wang
authors.forename: Olivier D
authors.initials: OD
authors.lastname: Defawe
authors.forename: Lindsey
authors.initials: L
authors.lastname: Baden
authors.forename: Paul
authors.initials: P
authors.lastname: Goepfert
authors.forename: Georgia D
authors.initials: GD
authors.lastname: Tomaras
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.forename: M Juliana
authors.initials: MJ
authors.lastname: McElrath
authors.forename: Lilian
authors.initials: L
authors.lastname: Saavedra
authors.forename: Chuen-Yen
authors.initials: CY
authors.lastname: Lau
authors.forename: Barney S
authors.initials: BS
authors.lastname: Graham
mesh_terms: D016915:AIDS Vaccines / Q000627:therapeutic use*; D000256:Adenoviridae / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D016207:Cytokines / Q000378:metabolism; D004247:DNA / Q000235:genetics*; D005260:Female; D005822:Genetic Vectors; D006678:HIV / Q000235:genetics*; D015658:HIV Infections / Q000517:prevention & control*; D006801:Humans; D007124:Immunoenzyme Techniques / Q000379:methods; D008297:Male; D008875:Middle Aged; D009500:Neutralization Tests; D010957:Plasmids / Q000378:metabolism; D013997:Time Factors; D019444:Vaccines, DNA / Q000627:therapeutic use*
chemical_list: D016915:AIDS Vaccines; D016207:Cytokines; D019444:Vaccines, DNA; D004247:DNA