Safety and immunogenicity of candidate vaccine M72/AS01E in adolescents in a TB endemic setting
2015
Penn-Nicholson, Adam | Geldenhuys, Hennie | Burny, Wivine | van der Most, Robbert | Day, Cheryl L. | Jongert, Erik | Moris, Philippe | Hatherill, Mark | Ofori-Anyinam, Opokua | Hanekom, Willem | Bollaerts, Anne | Demoitie, Marie-Ange | Kany Luabeya, Angelique Kany | De Ruymaeker, Evi | Tameris, Michele | Lapierre, Didier | Scriba, Thomas J.
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.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.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.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.
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