title: Safety and Immunogenicity of Adenovirus 35 Tuberculosis Vaccine Candidate in Adults with Active or Previous Tuberculosis. A Randomized Trial.
abstract: Administration of tuberculosis (TB) vaccines in participants with previous or current pulmonary TB may have the potential for causing harmful postvaccination immunologic (Koch-type) reactions.
  
  
  
  To assess the safety and immunogenicity of three dose levels of the AERAS-402 live, replication-deficient adenovirus 35-vectored TB candidate vaccine, containing three mycobacterial antigens, in individuals with current or previous pulmonary TB.
  
  
  
  We performed a phase II randomized, placebo-controlled, double-blinded dose-escalation study in an HIV-negative adult South African cohort (n = 72) with active pulmonary TB (on treatment for 1-4 mo) or pulmonary TB treated at least 12 months before study entry and considered cured. Safety endpoints included clinical assessment, flow volume curves, diffusing capacity of the lung for carbon monoxide, pulse oximetry, chest radiograph, and high-resolution thoracic computerized tomography scans. Cytokine expression by CD4 and CD8 T cells, after stimulation with Ag85A, Ag85B, and TB10.4 peptide pools, was examined by intracellular cytokine staining.
  
  
  
  No apparent temporal or dose-related changes in clinical status (specifically acute, Koch phenomenon-like reactions), lung function, or radiology attributable to vaccine were observed. Injection site reactions were mild or moderate. Hematuria (by dipstick only) occurred in 25 (41%) of 61 AERAS-402 recipients and 3 (27%) of 11 placebo recipients, although no gross hematuria was reported. AERAS-402 induced robust CD8+and moderate CD4+T-cell responses, mainly to Ag85B in both vaccine groups.
  
  
  
  Administration of the AERAS-402 candidate TB vaccine to participants with current or previous pulmonary TB induced a robust immune response and is not associated with clinically significant pulmonary complications. Clinical trial registered with www.clinicaltrials.gov (NCT 02414828) and in the South African National Clinical Trials Register ( www.sanctr.gov.za DOH 27-0808-2060).
authors.affiliation: 1 University of Cape Town Lung Institute, Division of Pulmonology, Department of Medicine.
authors.forename: Richard N
authors.initials: RN
authors.lastname: van Zyl-Smit
authors.affiliation: 1 University of Cape Town Lung Institute, Division of Pulmonology, Department of Medicine.
authors.forename: Aliasgar
authors.initials: A
authors.lastname: Esmail
authors.affiliation: 1 University of Cape Town Lung Institute, Division of Pulmonology, Department of Medicine.
authors.forename: Mary E
authors.initials: ME
authors.lastname: Bateman
authors.affiliation: 1 University of Cape Town Lung Institute, Division of Pulmonology, Department of Medicine.
authors.forename: Rodney
authors.initials: R
authors.lastname: Dawson
authors.affiliation: 2 UCLA Medical Centre, Los Angeles, California.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Goldin
authors.affiliation: 3 Department of Radiology, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands.
authors.forename: Eva
authors.initials: E
authors.lastname: van Rikxoort
authors.affiliation: 4 Crucell Holland B.V., a Janssen Pharmaceutical company of Johnson & Johnson, Leiden, the Netherlands.
authors.forename: Macaya
authors.initials: M
authors.lastname: Douoguih
authors.affiliation: 4 Crucell Holland B.V., a Janssen Pharmaceutical company of Johnson & Johnson, Leiden, the Netherlands.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Pau
authors.affiliation: 4 Crucell Holland B.V., a Janssen Pharmaceutical company of Johnson & Johnson, Leiden, the Netherlands.
authors.forename: Jerald C
authors.initials: JC
authors.lastname: Sadoff
authors.affiliation: 5 Aeras, Rockville, Maryland; and.
authors.forename: J Bruce
authors.initials: JB
authors.lastname: McClain
authors.affiliation: 5 Aeras, Rockville, Maryland; and.
authors.forename: Margaret Ann
authors.initials: MA
authors.lastname: Snowden
authors.affiliation: 5 Aeras, Rockville, Maryland; and.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Benko
authors.affiliation: 5 Aeras, Rockville, Maryland; and.
authors.forename: David A
authors.initials: DA
authors.lastname: Hokey
authors.affiliation: 5 Aeras, Rockville, Maryland; and.
authors.forename: Kathryn Tucker
authors.initials: KT
authors.lastname: Rutkowski
authors.affiliation: 5 Aeras, Rockville, Maryland; and.
authors.forename: Andrew
authors.initials: A
authors.lastname: Graves
authors.affiliation: 5 Aeras, Rockville, Maryland; and.
authors.forename: Barbara
authors.initials: B
authors.lastname: Shepherd
authors.affiliation: 5 Aeras, Rockville, Maryland; and.
authors.forename: Sadritdin
authors.initials: S
authors.lastname: Ishmukhamedov
authors.affiliation: 6 South African TB Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, Division of Immunology, Department of Pathology, and.|7 Vaccines for Africa Initiative, Division of Medical Microbiology, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
authors.forename: Benjamin M N
authors.initials: BMN
authors.lastname: Kagina
authors.affiliation: 6 South African TB Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, Division of Immunology, Department of Pathology, and.|8 Singapore Immunology Network, Agency for Science, Technology and Research, Singapore.
authors.forename: Brian
authors.initials: B
authors.lastname: Abel
authors.affiliation: 6 South African TB Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, Division of Immunology, Department of Pathology, and.
authors.forename: Willem A
authors.initials: WA
authors.lastname: Hanekom
authors.affiliation: 6 South African TB Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, Division of Immunology, Department of Pathology, and.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Scriba
authors.affiliation: 1 University of Cape Town Lung Institute, Division of Pulmonology, Department of Medicine.
authors.forename: Eric D
authors.identifier: 0000-0002-5064-5849
authors.initials: ED
authors.lastname: Bateman
mesh_terms: D000256:Adenoviridae; D000328:Adult; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008168:Lung / Q000000981:diagnostic imaging; D008176:Lung Volume Measurements; D008297:Male; D008875:Middle Aged; D010092:Oximetry; D013902:Radiography, Thoracic; D014057:Tomography, X-Ray Computed; D032581:Tuberculosis Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D014397:Tuberculosis, Pulmonary / Q000000981:diagnostic imaging / Q000276:immunology / Q000628:therapy*; D014613:Vaccines, Attenuated / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic; D055815:Young Adult
chemical_list: C000592463:AERAS-402; D016207:Cytokines; D032581:Tuberculosis Vaccines; D014613:Vaccines, Attenuated; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic
keywords: TB vaccine; pulmonary complications; tuberculosis; vaccine immunogenicity; vaccine safety