First-in-human trial of the post-exposure tuberculosis vaccine H56:IC31 in Mycobacterium tuberculosis infected and non-infected healthy adults.

摘要: Abstract Background H56:IC31 is a candidate tuberculosis vaccine comprising fusion protein of Ag85B, ESAT-6 and Rv2660c, formulated in IC31 adjuvant. This first-in-human, open label phase I trial assessed the safety immunogenicity healthy adults without or with Mycobacterium (M.tb) infection. Methods Low dose (15 μg H56 500 nmol IC31) high (50 μg H56, was administered intramuscularly thrice, at 56-day intervals. Antigen-specific T cell responses were measured by intracellular cytokine staining antibody ELISA. Results One hundred twenty-six subjects screened 25 enrolled vaccinated. No serious adverse events reported. Nine (36%) presented transient cardiovascular events. The induced antigen-specific IgG Th1 cytokine-expressing CD4+ cells. M.tb-infected vaccinees had higher frequencies H56-induced cells than uninfected vaccinees. vaccination more polyfunctional (IFN-γ+TNF-α+IL-2+) H56-specific compared vaccination. A striking increase IFN-γ-only-expressing cells, displaying CD45RA−CCR7− effector memory phenotype, emerged after second high-dose TNF-α+IL-2+ detected mostly low-dose vaccinees, predominantly expressed CD45RA−CCR7+ central phenotype. Our results support further clinical testing H56:IC31.