title: Safety and immunogenicity of candidate vaccine M72/AS01E in adolescents in a TB endemic setting.
abstract: BACKGROUND
  Vaccination that prevents tuberculosis (TB) disease, particularly in adolescents, would have the greatest impact on the global TB epidemic. Safety, reactogenicity and immunogenicity of the vaccine candidate M72/AS01E was evaluated in healthy, HIV-negative adolescents in a TB endemic region, regardless of Mycobacterium tuberculosis (M.tb) infection status.
  
  
  METHODS
  In a phase II, double-blind randomized, controlled study (NCT00950612), two doses of M72/AS01E or placebo were administered intramuscularly, one month apart. Participants were followed-up post-vaccination, for 6 months. M72-specific immunogenicity was evaluated by intracellular cytokine staining analysis of T cells and NK cells by flow cytometry.
  
  
  RESULTS
  No serious adverse events were recorded. M72/AS01E induced robust T cell and antibody responses, including antigen-dependent NK cell IFN-γ production. CD4 and CD8 T cell responses were sustained at 6 months post vaccination. Irrespective of M.tb infection status, vaccination induced a high frequency of M72-specific CD4 T cells expressing multiple combinations of Th1 cytokines, and low level IL-17. We observed rapid boosting of immune responses in M.tb-infected participants, suggesting natural infection acts as a prime to vaccination.
  
  
  CONCLUSIONS
  The clinically acceptable safety and immunogenicity profile of M72/AS01E in adolescents living in an area with high TB burden support the move to efficacy trials.
authors.affiliation: South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine & Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa. Electronic address: adam.penn-nicholson@uct.ac.za.
authors.forename: Adam
authors.initials: A
authors.lastname: Penn-Nicholson
authors.affiliation: South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine & Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa.
authors.forename: Hennie
authors.initials: H
authors.lastname: Geldenhuys
authors.affiliation: GSK Vaccines, Rixensart, Belgium.
authors.forename: Wivine
authors.initials: W
authors.lastname: Burny
authors.affiliation: GSK Vaccines, Rixensart, Belgium.
authors.forename: Robbert
authors.initials: R
authors.lastname: van der Most
authors.affiliation: South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine & Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa; Department of Global Health, Rollins School of Public Health, Atlanta, GA, USA; Emory Vaccine Center, Emory University, Atlanta, GA, USA.
authors.forename: Cheryl L
authors.initials: CL
authors.lastname: Day
authors.affiliation: GSK Vaccines, Rixensart, Belgium.
authors.forename: Erik
authors.initials: E
authors.lastname: Jongert
authors.affiliation: GSK Vaccines, Rixensart, Belgium.
authors.forename: Philippe
authors.initials: P
authors.lastname: Moris
authors.affiliation: South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine & Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa.
authors.forename: Mark
authors.initials: M
authors.lastname: Hatherill
authors.affiliation: GSK Vaccines, Rixensart, Belgium.
authors.forename: Opokua
authors.initials: O
authors.lastname: Ofori-Anyinam
authors.affiliation: South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine & Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa.
authors.forename: Willem
authors.initials: W
authors.lastname: Hanekom
authors.affiliation: GSK Vaccines, Rixensart, Belgium.
authors.forename: Anne
authors.initials: A
authors.lastname: Bollaerts
authors.affiliation: GSK Vaccines, Rixensart, Belgium.
authors.forename: Marie-Ange
authors.initials: MA
authors.lastname: Demoitie
authors.affiliation: South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa.
authors.forename: Angelique Kany
authors.initials: AK
authors.lastname: Kany Luabeya
authors.affiliation: GSK Vaccines, Rixensart, Belgium.
authors.forename: Evi
authors.initials: E
authors.lastname: De Ruymaeker
authors.affiliation: South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa.
authors.forename: Michele
authors.initials: M
authors.lastname: Tameris
authors.affiliation: GSK Vaccines, Rixensart, Belgium.
authors.forename: Didier
authors.initials: D
authors.lastname: Lapierre
authors.affiliation: South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Scriba
mesh_terms: D000293:Adolescent; D000942:Antigens, Bacterial / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D004311:Double-Blind Method; D004338:Drug Combinations; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D019353:Endemic Diseases; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007273:Injections, Intramuscular; D007694:Killer Cells, Natural / Q000276:immunology; D008050:Lipid A / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D008297:Male; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D010919:Placebos / Q000008:administration & dosage; D012503:Saponins / Q000008:administration & dosage / Q000009:adverse effects*; D013194:Staining and Labeling; D013601:T-Lymphocytes / Q000276:immunology; D016896:Treatment Outcome; D014376:Tuberculosis / Q000453:epidemiology* / Q000517:prevention & control*; D032581:Tuberculosis Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology
chemical_list: D000942:Antigens, Bacterial; D016207:Cytokines; D004338:Drug Combinations; D008050:Lipid A; D010919:Placebos; D012503:Saponins; D032581:Tuberculosis Vaccines; D022223:Vaccines, Subunit; C000592464:adjuvant system 01
keywords: Cytokine; M72/AS01(E); NK cell; T cell; Tuberculosis; Vaccine