Safety and immunogenicity of candidate vaccine M72/AS01E in adolescents in a TB endemic setting

Vaccine. 2015 Jul 31;33(32):4025-34. doi: 10.1016/j.vaccine.2015.05.088. Epub 2015 Jun 10.


Background: Vaccination that prevents tuberculosis (TB) disease, particularly in adolescents, would have the greatest impact on the global TB epidemic. Safety, reactogenicity and immunogenicity of the vaccine candidate M72/AS01E was evaluated in healthy, HIV-negative adolescents in a TB endemic region, regardless of Mycobacterium tuberculosis (M.tb) infection status.

Methods: In a phase II, double-blind randomized, controlled study (NCT00950612), two doses of M72/AS01E or placebo were administered intramuscularly, one month apart. Participants were followed-up post-vaccination, for 6 months. M72-specific immunogenicity was evaluated by intracellular cytokine staining analysis of T cells and NK cells by flow cytometry.

Results: No serious adverse events were recorded. M72/AS01E induced robust T cell and antibody responses, including antigen-dependent NK cell IFN-γ production. CD4 and CD8 T cell responses were sustained at 6 months post vaccination. Irrespective of M.tb infection status, vaccination induced a high frequency of M72-specific CD4 T cells expressing multiple combinations of Th1 cytokines, and low level IL-17. We observed rapid boosting of immune responses in M.tb-infected participants, suggesting natural infection acts as a prime to vaccination.

Conclusions: The clinically acceptable safety and immunogenicity profile of M72/AS01E in adolescents living in an area with high TB burden support the move to efficacy trials.

Keywords: Cytokine; M72/AS01(E); NK cell; T cell; Tuberculosis; Vaccine.

Publication types

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

MeSH terms

  • Adolescent
  • Antigens, Bacterial / immunology*
  • Cytokines / biosynthesis
  • Double-Blind Method
  • Drug Combinations
  • Drug-Related Side Effects and Adverse Reactions / epidemiology
  • Drug-Related Side Effects and Adverse Reactions / pathology
  • Endemic Diseases
  • Female
  • Flow Cytometry
  • Humans
  • Injections, Intramuscular
  • Killer Cells, Natural / immunology
  • Lipid A / administration & dosage
  • Lipid A / adverse effects
  • Lipid A / analogs & derivatives*
  • Male
  • Mycobacterium tuberculosis / immunology*
  • Placebos / administration & dosage
  • Saponins / administration & dosage
  • Saponins / adverse effects*
  • Staining and Labeling
  • T-Lymphocytes / immunology
  • Treatment Outcome
  • Tuberculosis / epidemiology*
  • Tuberculosis / prevention & control*
  • Tuberculosis Vaccines / administration & dosage
  • Tuberculosis Vaccines / adverse effects*
  • Tuberculosis Vaccines / immunology*
  • Vaccines, Subunit / administration & dosage
  • Vaccines, Subunit / adverse effects
  • Vaccines, Subunit / immunology


  • Antigens, Bacterial
  • Cytokines
  • Drug Combinations
  • Lipid A
  • Placebos
  • Saponins
  • Tuberculosis Vaccines
  • Vaccines, Subunit
  • adjuvant system 01

Associated data