The candidate tuberculosis vaccine Mtb72F/AS02 in PPD positive adults: a randomized controlled phase I/II study

Tuberculosis (Edinb). 2013 Mar;93(2):179-88. doi: 10.1016/j.tube.2012.10.011. Epub 2012 Dec 5.

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.

Trial registration: ClinicalTrials.gov identifier: NCT00146744.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Bacterial / biosynthesis
  • BCG Vaccine / immunology
  • CD4-Positive T-Lymphocytes / immunology
  • Dose-Response Relationship, Immunologic
  • Double-Blind Method
  • Female
  • Humans
  • Immunity, Cellular
  • Immunoglobulin G / biosynthesis
  • Interferon-gamma / biosynthesis
  • Male
  • Middle Aged
  • Mycobacterium tuberculosis / immunology
  • T-Lymphocyte Subsets / immunology
  • Tuberculin / immunology*
  • Tuberculosis / immunology*
  • Tuberculosis Vaccines / administration & dosage
  • Tuberculosis Vaccines / adverse effects
  • Tuberculosis Vaccines / immunology*
  • Vaccination / adverse effects
  • Young Adult

Substances

  • Antibodies, Bacterial
  • BCG Vaccine
  • Immunoglobulin G
  • Mtb72F-AS02A vaccine
  • Tuberculin
  • Tuberculosis Vaccines
  • Interferon-gamma

Associated data

  • ClinicalTrials.gov/NCT00146744