title: Induction of an Immune-Protective T-Cell Repertoire With Diverse Genetic Coverage by a Novel Viral-Vectored Tuberculosis Vaccine in Humans.
abstract: BACKGROUND
  Whether a candidate tuberculosis vaccine induces clinically relevant protective T-cell repertoires in humans will not be known until the completion of costly efficacy clinical trials.
  
  
  METHODS
  We have developed an integrated immunologic approach to investigate the clinical relevance of T cells induced by a novel tuberculosis vaccine in a phase 1 trial. This approach consists of screening for likely dominant T-cell epitopes, establishing antigen-specific memory T-cell lines for identifying CD8+and CD4+T-cell epitopes, determining the ability of vaccine-induced T cells to inhibit mycobacterial growth in infected cells, and examining the genetic diversity of HLA recognition and the clinical relevance of identified T-cell epitopes.
  
  
  RESULTS
  A single-dose immunization in BCG-primed adults with an adenovirus-based tuberculosis vaccine elicits a repertoire of memory T cells capable of recognizing multiple Ag85A epitopes. These T cells are polyfunctional and cytotoxic and can inhibit mycobacterial growth in infected target cells. Some identified T-cell epitopes are promiscuous and recognizable by the common HLA alleles. These epitopes are clinically relevant to the epitopes identified in people with latent Mycobacterium tuberculosis infection and treated patients with tuberculosis.
  
  
  CONCLUSIONS
  These data support further clinical development of this candidate vaccine. Our approach helps fill the gap in clinical tuberculosis vaccine development.
authors.affiliation: McMaster Immunology Research Centre.|Department of Pathology and Molecular Medicine.|Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Canada.
authors.forename: Mangalakumari
authors.initials: M
authors.lastname: Jeyanathan
authors.affiliation: McMaster Immunology Research Centre.|Department of Pathology and Molecular Medicine.|Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Canada.
authors.forename: Daniela
authors.initials: D
authors.lastname: Damjanovic
authors.affiliation: McMaster Immunology Research Centre.|Department of Pathology and Molecular Medicine.|Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Canada.
authors.forename: Yushi
authors.initials: Y
authors.lastname: Yao
authors.affiliation: McMaster Immunology Research Centre.|Department of Pathology and Molecular Medicine.|Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Canada.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Bramson
authors.affiliation: Department of Pathology and Molecular Medicine.|Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Canada.
authors.forename: Fiona
authors.initials: F
authors.lastname: Smaill
authors.affiliation: McMaster Immunology Research Centre.|Department of Pathology and Molecular Medicine.|Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Canada.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Xing
mesh_terms: D000217:Acyltransferases / Q000235:genetics / Q000276:immunology; D000256:Adenoviridae / Q000235:genetics*; D000328:Adult; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology; D004337:Drug Carriers; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology / Q000517:prevention & control*; D032581:Tuberculosis Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D000942:Antigens, Bacterial; D004337:Drug Carriers; D018984:Epitopes, T-Lymphocyte; D032581:Tuberculosis Vaccines; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic; D000217:Acyltransferases; C112580:antigen 85A, Mycobacterium tuberculosis
keywords: CD8+ T cells; T cells; clinical trial; epitopes; tuberculosis; vaccine; viral vector