title: The novel tuberculosis vaccine, AERAS-402, induces robust and polyfunctional CD4+ and CD8+ T cells in adults.
abstract: BACKGROUND
  AERAS-402 is a novel tuberculosis vaccine designed to boost immunity primed by bacillus Calmette-Guérin (BCG), the only licensed vaccine.
  
  
  OBJECTIVE
  We investigated the safety and immunogenicity of AERAS-402 in healthy Mycobacterium tuberculosis-uninfected BCG-vaccinated adults from a tuberculosis-endemic region of South Africa.
  
  
  METHODS
  Escalating doses of AERAS-402 vaccine were administered intramuscularly to each of three groups of healthy South African BCG-vaccinated adults, and a fourth group received two injections of the maximal dose. Participants were monitored for 6 months, with all adverse effects documented. Vaccine-induced CD4(+) and CD8(+) T-cell immunity was characterized by an intracellular cytokine staining assay of whole blood and peripheral blood mononuclear cells.
  
  
  RESULTS
  AERAS-402 was well tolerated, and no vaccine-related serious adverse events were recorded. The vaccine induced a robust CD4(+) T-cell response dominated by cells coexpressing IFN-gamma, tumor necrosis factor-alpha, and IL-2 ("polyfunctional" cells). AERAS-402 also induced a potent CD8(+) T-cell response, characterized by cells expressing IFN-gamma and/or tumor necrosis factor-alpha, which persisted for the duration of the study.
  
  
  CONCLUSIONS
  Vaccination with AERAS-402 is safe and immunogenic in healthy adults. The immunity induced by the vaccine appears promising: polyfunctional T cells are thought to be important for protection against intracellular pathogens such as Mycobacterium tuberculosis, and evidence is accumulating that CD8(+) T cells are also important. AERAS-402 induced a robust and durable CD8(+) T-cell response, which appears extremely promising. Clinical trial registered with www.sanctr.gov.za (NHREC no. 1381).
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, UCT Health Sciences, Anzio Road, Observatory 7925, Cape Town, South Africa.
authors.forename: Brian
authors.initials: B
authors.lastname: Abel
authors.forename: Michele
authors.initials: M
authors.lastname: Tameris
authors.forename: Nazma
authors.initials: N
authors.lastname: Mansoor
authors.forename: Sebastian
authors.initials: S
authors.lastname: Gelderbloem
authors.forename: Jane
authors.initials: J
authors.lastname: Hughes
authors.forename: Deborah
authors.initials: D
authors.lastname: Abrahams
authors.forename: Lebohang
authors.initials: L
authors.lastname: Makhethe
authors.forename: Mzwandile
authors.initials: M
authors.lastname: Erasmus
authors.forename: Marwou
authors.initials: M
authors.lastname: de Kock
authors.forename: Linda
authors.initials: L
authors.lastname: van der Merwe
authors.forename: Anthony
authors.initials: A
authors.lastname: Hawkridge
authors.forename: Ashley
authors.initials: A
authors.lastname: Veldsman
authors.forename: Mark
authors.initials: M
authors.lastname: Hatherill
authors.forename: Giulia
authors.initials: G
authors.lastname: Schirru
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Pau
authors.forename: Jenny
authors.initials: J
authors.lastname: Hendriks
authors.forename: Gerrit Jan
authors.initials: GJ
authors.lastname: Weverling
authors.forename: Jaap
authors.initials: J
authors.lastname: Goudsmit
authors.forename: Donata
authors.initials: D
authors.lastname: Sizemore
authors.forename: J Bruce
authors.initials: JB
authors.lastname: McClain
authors.forename: Margaret
authors.initials: M
authors.lastname: Goetz
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Gearhart
authors.forename: Hassan
authors.initials: H
authors.lastname: Mahomed
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Hussey
authors.forename: Jerald C
authors.initials: JC
authors.lastname: Sadoff
authors.forename: Willem A
authors.initials: WA
authors.lastname: Hanekom
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D013019:South Africa; D032581:Tuberculosis Vaccines / Q000276:immunology / Q000627:therapeutic use*; D019444:Vaccines, DNA; D055815:Young Adult
chemical_list: C000592463:AERAS-402; D032581:Tuberculosis Vaccines; D019444:Vaccines, DNA