Safety and immunogenicity of candidate vaccine M72/AS01E in adolescents in a TB endemic setting |
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| Affiliation: | 1. 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;2. GSK Vaccines, Rixensart, Belgium;3. Department of Global Health, Rollins School of Public Health, Atlanta, GA, USA;4. Emory Vaccine Center, Emory University, Atlanta, GA, USA;1. 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;2. GSK Vaccines, Rixensart, Belgium |
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| Abstract: | 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. |
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| Keywords: | Tuberculosis Vaccine T cell NK cell Cytokine |
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