title: A phase 1/2 study of a multiclade HIV-1 DNA plasmid prime and recombinant adenovirus serotype 5 boost vaccine in HIV-Uninfected East Africans (RV 172).
abstract: BACKGROUND
  Human immunodeficiency virus (HIV) vaccine development remains a global priority. We describe the safety and immunogenicity of a multiclade DNA vaccine prime with a replication-defective recombinant adenovirus serotype 5 (rAd5) boost.
  
  
  METHODS
  The vaccine is a 6-plasmid mixture encoding HIV envelope (env) subtypes A, B, and C and subtype B gag, pol, and nef, and an rAd5 expressing identical genes, with the exception of nef. Three hundred and twenty-four participants were randomized to receive placebo (n=138), a single dose of rAd5 at 10(10) (n = 24) or 10(11) particle units (n = 24), or DNA at 0, 1, and 2 months, followed by rAd5 at either 10(10) (n= 114) or 10(11) particle units (n = 24) boosting at 6 months. Participants were followed up for 24 weeks after the final vaccination.
  
  
  RESULTS
  The vaccine was safe and well tolerated. HIV-specific T cell responses were detected in 63% of vaccinees. Titers of preexisting Ad5 neutralizing antibody did not affect the frequency and magnitude of T cell responses in prime-boost recipients but did affect the response rates in participants that received rAd5 alone (P = .037).
  
  
  CONCLUSIONS
  The DNA/rAd5 vaccination regimen was safe and induced HIV type 1 multi-clade T cell responses, which were not significantly affected by titers of preexisting rAd5 neutralizing antibody. Trial Registration. ClinicalTrials.gov identifier: NCT00123968 .
authors.affiliation: Makerere University Walter Reed Project, Kampala, Uganda.
authors.forename: Hannah
authors.initials: H
authors.lastname: Kibuuka
authors.forename: Robert
authors.initials: R
authors.lastname: Kimutai
authors.forename: Leonard
authors.initials: L
authors.lastname: Maboko
authors.forename: Fred
authors.initials: F
authors.lastname: Sawe
authors.forename: Mirjam S
authors.initials: MS
authors.lastname: Schunk
authors.forename: Arne
authors.initials: A
authors.lastname: Kroidl
authors.forename: Douglas
authors.initials: D
authors.lastname: Shaffer
authors.forename: Leigh Anne
authors.initials: LA
authors.lastname: Eller
authors.forename: Rukia
authors.initials: R
authors.lastname: Kibaya
authors.forename: Michael A
authors.initials: MA
authors.lastname: Eller
authors.forename: Karin B
authors.initials: KB
authors.lastname: Schindler
authors.forename: Alexandra
authors.initials: A
authors.lastname: Schuetz
authors.forename: Monica
authors.initials: M
authors.lastname: Millard
authors.forename: Jason
authors.initials: J
authors.lastname: Kroll
authors.forename: Len
authors.initials: L
authors.lastname: Dally
authors.forename: Michael
authors.initials: M
authors.lastname: Hoelscher
authors.forename: Robert
authors.initials: R
authors.lastname: Bailer
authors.forename: Josephine H
authors.initials: JH
authors.lastname: Cox
authors.forename: Mary
authors.initials: M
authors.lastname: Marovich
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Birx
authors.forename: Barney S
authors.initials: BS
authors.lastname: Graham
authors.forename: Nelson L
authors.initials: NL
authors.lastname: Michael
authors.forename: Mark S
authors.initials: MS
authors.lastname: de Souza
authors.forename: Merlin L
authors.initials: ML
authors.lastname: Robb
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000235:genetics / Q000276:immunology; D000256:Adenoviridae / Q000235:genetics / Q000276:immunology*; D000293:Adolescent; D000328:Adult; D000351:Africa, Eastern; D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D004279:DNA, Viral / Q000235:genetics / Q000276:immunology*; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D054298:Human Immunodeficiency Virus Proteins / Q000235:genetics / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010957:Plasmids / Q000235:genetics / Q000276:immunology*; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000009:adverse effects / Q000235:genetics / Q000276:immunology; D055815:Young Adult
chemical_list: D016915:AIDS Vaccines; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000956:Antigens, Viral; D004279:DNA, Viral; D054298:Human Immunodeficiency Virus Proteins; D019444:Vaccines, DNA; D007371:Interferon-gamma