• Adam Penn-Nicholson, Hennie Geldenhuys, Wivine Burny, Robbert van der Most, Cheryl L Day, Erik Jongert, Philippe Moris, Mark Hatherill, Opokua Ofori-Anyinam, Willem Hanekom, Vaccine Study Team, Anne Bollaerts, Marie-Ange Demoitie, Kany Luabeya Angelique Kany AK South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, Department of Paediatrics and Child , Evi De Ruymaeker, Michele Tameris, Didier Lapierre, and Thomas J Scriba.
• South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine & Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa. Electronic address: adam.penn-nicholson@uct.ac.za.
• Vaccine. 2015 Jul 31; 33 (32): 4025-34.

BackgroundVaccination 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.MethodsIn 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.ResultsNo 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.ConclusionsThe 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.Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

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