title: First-in-man open clinical trial of a combined rdESAT-6 and rCFP-10 tuberculosis specific skin test reagent.
abstract: BACKGROUND
  Tuberculin is still the only available skin test reagent for the diagnosis of mycobacterial infection. The product has a remarkable sensitivity, but poor specificity. Previous studies, including two human phase I clinical trials, have indicated that rdESAT-6 has a potential as an improved skin test reagent. Animal studies have shown that the sensitivity may be increased by inclusion of the genetically related CFP-10 antigen in the preparation without loosing specificity.
  
  
  METHODS
  In this study a Lactococcus fermented, recombinant skin test reagent consisting of a 1ratio1 wt/wt of rdESAT-6 and CFP-10 was manufactured according to GMP standards and tested for the first time in 42 healthy adult volunteers. The two doses of 0.01 microg or 0.1 microg were injected intradermally by the Mantoux technique with 6 or 12 weeks interval. No serious adverse events and only mild adverse reactions were reported. The reagent elicited a positive skin test reaction after the first injection in one participant, who most likely was latently infected with M. tuberculosis as indicated by an appreciable IFN gamma response just below the Quantiferon(R) cut-off level at the screening visit. None of the remaining participants in the four groups had any skin test reactions and sensitisation by the reagent could therefore be excluded.
  
  
  CONCLUSIONS
  The investigational skin test reagent rdESAT-6 and CFP-10 appeared safe and non-sensitising in this first-in-man clinical trial in human volunteers and can now be tested in larger clinical trials involving individuals with latent M. tuberculosis infection or active TB disease.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00793702.
authors.affiliation: Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Winnie
authors.initials: W
authors.lastname: Bergstedt
authors.forename: Pernille N
authors.initials: PN
authors.lastname: Tingskov
authors.forename: Birgit
authors.initials: B
authors.lastname: Thierry-Carstensen
authors.forename: Søren T
authors.initials: ST
authors.lastname: Hoff
authors.forename: Henrik
authors.initials: H
authors.lastname: Aggerbeck
authors.forename: Vibeke O
authors.initials: VO
authors.lastname: Thomsen
authors.forename: Peter
authors.initials: P
authors.lastname: Andersen
authors.forename: Aase B
authors.initials: AB
authors.lastname: Andersen
mesh_terms: D000328:Adult; D000942:Antigens, Bacterial / Q000009:adverse effects; D001426:Bacterial Proteins / Q000009:adverse effects; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D011994:Recombinant Proteins / Q000009:adverse effects; D012680:Sensitivity and Specificity; D014374:Tuberculin Test / Q000379:methods*; D014376:Tuberculosis / Q000175:diagnosis*
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C117940:CFP-10 protein, Mycobacterium tuberculosis; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D011994:Recombinant Proteins; D007371:Interferon-gamma