title: A new recombinant bacille Calmette-Guérin vaccine safely induces significantly enhanced tuberculosis-specific immunity in human volunteers.
abstract: BACKGROUND
  One strategy for improving anti-tuberculosis (TB) vaccination involves the use of recombinant bacille Calmette-Guérin (rBCG) overexpressing protective TB antigens. rBCG30, which overexpresses the Mycobacterium tuberculosis secreted antigen Ag85b, was the first rBCG shown to induce significantly greater protection against TB in animals than parental BCG.
  
  
  METHODS
  We report here the first double-blind phase 1 trial of rBCG30 in 35 adults randomized to receive either rBCG30 or parental Tice BCG intradermally. Clinical reactogenicity was assessed, and state-of-the-art immunological assays were used to study Ag85b-specific immune responses induced by both vaccines.
  
  
  RESULTS
  Similar clinical reactogenicity occurred with both vaccines. rBCG30 induced significantly increased Ag85b-specific T cell lymphoproliferation, interferon (IFN)-gamma secretion, IFN-gamma enzyme-linked immunospot responses, and direct ex vivo intracellular IFN-gamma responses. Additional flow cytometry studies measuring carboxyfluorescein succinimidyl ester dilution and intracellular cytokine production demonstrated that rBCG30 significantly enhanced the population of Ag85b-specific CD4(+) and CD8(+) T cells capable of concurrent expansion and effector function. More importantly, rBCG30 significantly increased the number of Ag85b-specific T cells capable of inhibiting intracellular mycobacteria.
  
  
  CONCLUSIONS
  These results provide proof of principal that rBCG can safely enhance human TB immunity and support further development of rBCG overexpressing Ag85b for TB vaccination.
authors.affiliation: Department of Internal Medicine and Molecular Biology, Saint Louis University Medical Center, and Center for Vaccine Development, Saint Louis, MO 63104, USA. hoftdf@slu.edu
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Hoft
authors.forename: Azra
authors.initials: A
authors.lastname: Blazevic
authors.forename: Getahun
authors.initials: G
authors.lastname: Abate
authors.forename: Willem A
authors.initials: WA
authors.lastname: Hanekom
authors.forename: Gilla
authors.initials: G
authors.lastname: Kaplan
authors.forename: Jorge H
authors.initials: JH
authors.lastname: Soler
authors.forename: Frank
authors.initials: F
authors.lastname: Weichold
authors.forename: Larry
authors.initials: L
authors.lastname: Geiter
authors.forename: Jerald C
authors.initials: JC
authors.lastname: Sadoff
authors.forename: Marcus A
authors.initials: MA
authors.lastname: Horwitz
mesh_terms: D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D001500:BCG Vaccine / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology* / Q000592:standards*; D018984:Epitopes, T-Lymphocyte; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D008297:Male; D009169:Mycobacterium tuberculosis / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D014376:Tuberculosis / Q000517:prevention & control*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology / Q000592:standards; D055815:Young Adult
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001500:BCG Vaccine; D018984:Epitopes, T-Lymphocyte; D011993:Recombinant Fusion Proteins; D014614:Vaccines, Synthetic; D007371:Interferon-gamma