title: A phase IIa trial of the new tuberculosis vaccine, MVA85A, in HIV- and/or Mycobacterium tuberculosis-infected adults.
abstract: BACKGROUND
  Novel tuberculosis (TB) vaccines should be safe and effective in populations infected with Mycobacterium tuberculosis (M.tb) and/or HIV for effective TB control.
  
  
  OBJECTIVE
  To determine the safety and immunogenicity of MVA85A, a novel TB vaccine, among M.tb- and/or HIV-infected persons in a setting where TB and HIV are endemic.
  
  
  METHODS
  An open-label, phase IIa trial was conducted in 48 adults with M.tb and/or HIV infection. Safety and immunogenicity were analyzed up to 52 weeks after intradermal vaccination with 5 × 10(7) plaque-forming units of MVA85A. Specific T-cell responses were characterized by IFN-γ enzyme-linked immunospot and whole blood intracellular cytokine staining assays.
  
  
  RESULTS
  MVA85A was well tolerated and no vaccine-related serious adverse events were recorded. MVA85A induced robust and durable response of mostly polyfunctional CD4(+) T cells, coexpressing IFN-γ, tumor necrosis factor-α, and IL-2. Magnitudes of pre- and postvaccination T-cell responses were lower in HIV-infected, compared with HIV-uninfected, vaccinees. No significant effect of antiretroviral therapy on immunogenicity of MVA85A was observed.
  
  
  CONCLUSIONS
  MVA85A was safe and immunogenic in persons with HIV and/or M.tb infection. These results support further evaluation of safety and efficacy of this vaccine for prevention of TB in these target populations.
authors.affiliation: South African Tuberculosis Vaccine Initiative, Institute of Infectious Diseases and Molecular Medicine, and School of Child and Adolescent Health, University of Cape Town, Cape Town, South Africa. thomas.scriba@uct.ac.za
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Scriba
authors.forename: Michele
authors.initials: M
authors.lastname: Tameris
authors.forename: Erica
authors.initials: E
authors.lastname: Smit
authors.forename: Linda
authors.initials: L
authors.lastname: van der Merwe
authors.forename: E Jane
authors.initials: EJ
authors.lastname: Hughes
authors.forename: Blessing
authors.initials: B
authors.lastname: Kadira
authors.forename: Katya
authors.initials: K
authors.lastname: Mauff
authors.forename: Sizulu
authors.initials: S
authors.lastname: Moyo
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Brittain
authors.forename: Alison
authors.initials: A
authors.lastname: Lawrie
authors.forename: Humphrey
authors.initials: H
authors.lastname: Mulenga
authors.forename: Marwou
authors.initials: M
authors.lastname: de Kock
authors.forename: Lebohang
authors.initials: L
authors.lastname: Makhethe
authors.forename: Esme
authors.initials: E
authors.lastname: Janse van Rensburg
authors.forename: Sebastian
authors.initials: S
authors.lastname: Gelderbloem
authors.forename: Ashley
authors.initials: A
authors.lastname: Veldsman
authors.forename: Mark
authors.initials: M
authors.lastname: Hatherill
authors.forename: Hendrik
authors.initials: H
authors.lastname: Geldenhuys
authors.forename: Adrian V S
authors.initials: AV
authors.lastname: Hill
authors.forename: Anthony
authors.initials: A
authors.lastname: Hawkridge
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Hussey
authors.forename: Willem A
authors.initials: WA
authors.lastname: Hanekom
authors.forename: Helen
authors.initials: H
authors.lastname: McShane
authors.forename: Hassan
authors.initials: H
authors.lastname: Mahomed
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000517:prevention & control; D000293:Adolescent; D000328:Adult; D018791:CD4 Lymphocyte Count; D005260:Female; D015658:HIV Infections / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D008297:Male; D008875:Middle Aged; D032581:Tuberculosis Vaccines / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D014397:Tuberculosis, Pulmonary / Q000276:immunology / Q000517:prevention & control / Q000628:therapy*; D019444:Vaccines, DNA; D019562:Viral Load; D014765:Viral Vaccines / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: C549320:MVA 85A; D032581:Tuberculosis Vaccines; D019444:Vaccines, DNA; D014765:Viral Vaccines