title: The safety and immunogenicity of an adenovirus type 35-vectored TB vaccine in HIV-infected, BCG-vaccinated adults with CD4(+) T cell counts >350 cells/mm(3).
abstract: BACKGROUND
  The safety and immunogenicity of a replication deficient adenovirus serotype 35 tuberculosis (TB) vaccine containing gene inserts for Antigens (Ag) 85A, Ag85B and TB10.4 (AERAS-402/AD35.TB-S) was evaluated in previously BCG vaccinated, HIV-infected South African adults with baseline CD4 counts >350 cells/mm(3).
  
  
  METHODS
  Subjects were randomized (1:1) to receive two doses of either intramuscular AERAS-402/AD35.TB-S or placebo at month 0 and at month 1. Participants were monitored for adverse events 28 days after each vaccination and for serious adverse events over 12 months. CD4(+) and CD8(+) T-cell and antibody responses to vaccine antigens were evaluated post first and second vaccination.
  
  
  RESULTS
  26 subjects were randomly assigned to receive AERAS-402/AD35.TB-S (N=13) or placebo (N=13). The mean age was 29.0 years, all were Black-African, 88.5% were female, 46.2% were QuantiFERON Test (QFT) positive at baseline, and the median CD4 count was 559.5 cells/mm(3), all similar by treatment group. All subjects received their first vaccination and 24 subjects received their second vaccination. Injection site reactions and some systemic reactions were reported more commonly in the AERAS-402/AD35.TB-S versus placebo recipients. AERAS-402/AD35.TB-S did not appear to influence CD4 counts and HIV-1 viral load over the course of study follow-up. AERAS-402/AD35.TB-S induced a mixed CD4(+) T-cell and CD8(+) T-cell responses to Ag85B. The CD4(+) T-cell responses peaked to Ag85A and Ag85B 14 days after the second vaccination and had declined by Day 182. AERAS-402/AD35.TB-S predominantly induced CD4(+) T-cells expressing three (IFN-γ, TNF, IL-2) or two (IL-2 and TNF) cytokines, two weeks after the last vaccination, which did not differ by baseline Quantiferon test status. AERAS-402/AD35.TB-S induced strong Ag85A and Ag85B specific antibody responses, particularly after the second vaccination.
  
  
  CONCLUSIONS
  AERAS-402/AD35.TB-S was well tolerated, safe and induced predominantly polyfunctional CD4(+) and CD8(+) T-cell responses to vaccine.
authors.affiliation: Aurum Institute, Johannesburg, South Africa; School of Public Health, University of Witwatersrand, Johannesburg, South Africa. Electronic address: gchurchyard@auruminstitute.org.
authors.forename: Gavin John
authors.initials: GJ
authors.lastname: Churchyard
authors.affiliation: Aeras, Rockville, MD, United States.
authors.forename: Margaret Ann
authors.initials: MA
authors.lastname: Snowden
authors.affiliation: Aeras, Rockville, MD, United States.
authors.forename: David
authors.initials: D
authors.lastname: Hokey
authors.affiliation: Aeras, Rockville, MD, United States.
authors.forename: Veerabadran
authors.initials: V
authors.lastname: Dheenadhayalan
authors.affiliation: Aeras, Rockville, MD, United States.
authors.forename: J Bruce
authors.initials: JB
authors.lastname: McClain
authors.affiliation: Crucell Holland N.V., Leiden, The Netherlands.
authors.forename: Macaya
authors.initials: M
authors.lastname: Douoguih
authors.affiliation: Crucell Holland N.V., Leiden, The Netherlands.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Pau
authors.affiliation: Crucell Holland N.V., Leiden, The Netherlands.
authors.forename: Jerry
authors.initials: J
authors.lastname: Sadoff
authors.affiliation: Aeras, Rockville, MD, United States.
authors.forename: Bernard
authors.initials: B
authors.lastname: Landry
mesh_terms: D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000276:immunology*; D001500:BCG Vaccine / Q000276:immunology*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes; D004311:Double-Blind Method; D005260:Female; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D007273:Injections, Intramuscular; D007371:Interferon-gamma / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology; D013019:South Africa; D014376:Tuberculosis / Q000517:prevention & control*; D032581:Tuberculosis Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D014611:Vaccination; D019444:Vaccines, DNA; D019562:Viral Load; D055815:Young Adult
chemical_list: C000592463:AERAS-402; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001500:BCG Vaccine; D007376:Interleukin-2; D032581:Tuberculosis Vaccines; D014409:Tumor Necrosis Factor-alpha; D019444:Vaccines, DNA; D007371:Interferon-gamma
keywords: Clinicaltrials.gov (NHREC no. NCT01017536); DOH-27-0809-2497; HIV; Immunogenicity; Safety; Tuberculosis; Vaccines