title: The candidate tuberculosis vaccine Mtb72F/AS02 in PPD positive adults: a randomized controlled phase I/II study.
abstract: Prevention of tuberculosis (TB) through vaccination would substantially reduce the global TB burden. Mtb72F/AS02 is a candidate TB vaccine shown to be immunogenic and well tolerated in PPD-negative adults. We evaluated the safety and immunogenicity of Mtb72F/AS02 in Mycobacterium-primed adults (BCG-vaccinated, or infected adults who had received post-exposure chemoprophylaxis or treatment for pulmonary TB disease). In this observer-blind controlled trial, 20 BCG-vaccinated adults and 18 adults previously infected with Mycobacterium tuberculosis (Mtb), were randomized 3:1 to receive three doses of Mtb72F/AS02 or AS02 at one-month intervals, and followed for 6 months post third vaccination. Mtb72F/AS02 was well tolerated in BCG-vaccinated adults, and tended to be more reactogenic in Mtb-infected adults. Adverse events were mainly self-limiting, resolving without sequelae. No serious adverse events were reported. The adverse events in Mtb72F/AS02 vaccinees were not clearly associated with vaccine-induced responses (as assessed by proinflammatory cytokines, total IgE and C-reactive protein levels). No Th2 T-cell responses, or vaccine-induced T-cell responses to Mtb antigens (CFP-10/PPD/ESAT-6) were detected by ICS. In both cohorts, Mtb72F/AS02 induced persistent polyfunctional Mtb72F-specific CD4(+) T-cell responses and anti-Mtb72F humoral responses. IFN-γ was detectable in serum one day post each vaccination. Further evaluation of the candidate vaccine, Mtb72F/AS02, is warranted.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier: NCT00146744.
authors.affiliation: Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois (CHUV-BH19), Rue du Bugnon, CH-1011 Lausanne, Switzerland. Francois.Spertini@chuv.ch
authors.forename: François
authors.initials: F
authors.lastname: Spertini
authors.forename: Régine
authors.initials: R
authors.lastname: Audran
authors.forename: Floriana
authors.initials: F
authors.lastname: Lurati
authors.forename: Opokua
authors.initials: O
authors.lastname: Ofori-Anyinam
authors.forename: Frédéric
authors.initials: F
authors.lastname: Zysset
authors.forename: Pierre
authors.initials: P
authors.lastname: Vandepapelière
authors.forename: Philippe
authors.initials: P
authors.lastname: Moris
authors.forename: Marie-Ange
authors.initials: MA
authors.lastname: Demoitié
authors.forename: Pascal
authors.initials: P
authors.lastname: Mettens
authors.forename: Carlota
authors.initials: C
authors.lastname: Vinals
authors.forename: Ilse
authors.initials: I
authors.lastname: Vastiau
authors.forename: Erik
authors.initials: E
authors.lastname: Jongert
authors.forename: Joe
authors.initials: J
authors.lastname: Cohen
authors.forename: W Ripley
authors.initials: WR
authors.lastname: Ballou
mesh_terms: D000293:Adolescent; D000328:Adult; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D001500:BCG Vaccine / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D007074:Immunoglobulin G / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014373:Tuberculin / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology*; D032581:Tuberculosis Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D014611:Vaccination / Q000009:adverse effects; D055815:Young Adult
chemical_list: D000907:Antibodies, Bacterial; D001500:BCG Vaccine; D007074:Immunoglobulin G; C539343:Mtb72F-AS02A vaccine; D014373:Tuberculin; D032581:Tuberculosis Vaccines; D007371:Interferon-gamma