title: H1:IC31 vaccination is safe and induces long-lived TNF-α+IL-2+CD4 T cell responses in M. tuberculosis infected and uninfected adolescents: A randomized trial.
abstract: Control of the tuberculosis epidemic requires a novel vaccine that is effective in preventing tuberculosis in adolescents, a key target population for vaccination against TB.
  
  
  
  Healthy adolescents, stratified by M. tuberculosis-infection status, were enrolled into this observer-blinded phase II clinical trial of the protein-subunit vaccine candidate, H1:IC31, comprising a fusion protein (H1) of Ag85B and ESAT-6, formulated with the IC31 adjuvant. Local and systemic adverse events and induced T cell responses were measured after one or two administrations of either 15μg or 50μg of the H1 protein.
  
  
  
  Two hundred and forty participants were recruited and followed up for 224days. No notable safety events were observed regardless of H1 dose or vaccination schedule. H1:IC31 vaccination induced antigen-specific CD4 T cells, co-expressing IFN-γ, TNF-α and/or IL-2. H1:IC31 vaccination of M.tb-uninfected individuals preferentially drove the emergence of Ag85B and ESAT-6 specific TNF-α+IL-2+CD4 T cells, while H1:IC31 vaccination of M.tb-infected individuals resulted in the expansion of Ag85B-specific but not ESAT-6-specific TNF-α+IL-2+CD4 T cells.
  
  
  
  H1:IC31 was safe and immunogenic in uninfected and M.tb-infected adolescents. Two administrations of the 15μg H1:IC31 dose induced the greatest magnitude immune response, and was considered optimal (South African National Clinical Trials Register, DoH-27-0612-3947; Pan African Clinical Trial Registry, PACTR201403000464306).
authors.affiliation: South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town, South Africa.
authors.forename: Helen
authors.initials: H
authors.lastname: Mearns
authors.affiliation: South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town, South Africa.
authors.forename: Hennie D
authors.initials: HD
authors.lastname: Geldenhuys
authors.affiliation: South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town, South Africa.
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Kagina
authors.affiliation: South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town, South Africa.
authors.forename: Munyaradzi
authors.initials: M
authors.lastname: Musvosvi
authors.affiliation: Department of Statistical Sciences, University of Cape Town, South Africa.
authors.forename: Francesca
authors.initials: F
authors.lastname: Little
authors.affiliation: South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town, South Africa.
authors.forename: Frances
authors.initials: F
authors.lastname: Ratangee
authors.affiliation: South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town, South Africa.
authors.forename: Hassan
authors.initials: H
authors.lastname: Mahomed
authors.affiliation: South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town, South Africa.
authors.forename: Willem A
authors.initials: WA
authors.lastname: Hanekom
authors.affiliation: Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Søren T
authors.initials: ST
authors.lastname: Hoff
authors.affiliation: Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Morten
authors.initials: M
authors.lastname: Ruhwald
authors.affiliation: Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Kromann
authors.affiliation: Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Bang
authors.affiliation: South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town, South Africa.
authors.forename: Mark
authors.initials: M
authors.lastname: Hatherill
authors.affiliation: Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Andersen
authors.affiliation: South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town, South Africa. Electronic address: Thomas.scriba@uct.ac.za.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Scriba
mesh_terms: D000217:Acyltransferases / Q000235:genetics / Q000276:immunology*; D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000009:adverse effects*; D000293:Adolescent; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002648:Child; D004338:Drug Combinations; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism; D008297:Male; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage / Q000009:adverse effects*; D009842:Oligopeptides / Q000008:administration & dosage / Q000009:adverse effects*; D016037:Single-Blind Method; D032581:Tuberculosis Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000235:genetics / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D004338:Drug Combinations; C093276:ESAT-6 protein, Mycobacterium tuberculosis; C544002:IC31 adjuvant; D007376:Interleukin-2; D009838:Oligodeoxyribonucleotides; D009842:Oligopeptides; D032581:Tuberculosis Vaccines; D014409:Tumor Necrosis Factor-alpha; D014614:Vaccines, Synthetic; D000217:Acyltransferases; C121433:antigen 85B, Mycobacterium tuberculosis
keywords: Adolescents; Ag85B; Clinical trial; ESAT-6; H1:IC31; Mycobacterium tuberculosis; Randomised; Vaccine