The most prevalent subset was IL-2/TNF-α double producing CD4 T-cells, Vorinostat cost and significantly increased frequencies

of these cells were seen in the intermediate and high adjuvant groups compared to the non-adjuvant group (Fig. 4C). Responses were also detected in the triple positive subset and TNF-α single positive subset, but neither reached significance. No significant IL-17 responses to antigenic stimulation were detected (data not shown). No CD8 T-cell responses were observed following Ag85B or ESAT-6 stimulation (data not shown). No statistically significant changes from baseline were seen in any of the vaccination groups in IgG anti-Ag85B-ESAT-6 specific antibody titer (data not shown, methods

in online supplement). QFT was performed at baseline at week 32, and 150 weeks after the last vaccination. All subjects were negative before vaccination (as per the inclusion criteria) and none in the non-adjuvanted group became QFT positive. However introducing CAF01 adjuvant in the vaccine caused 3 out of 8 (38%) individuals in the low CAF01 group to convert to a positive test, 6 out of 10 (60%) in the intermediate CAF01 group and 3 out of 8 (38%) in the high adjuvant group (Fig. 5). All but two of the QFT converters had reverted to negative at week 150. One QFT converter was lost to the extended follow up. This report describes the first clinical trial in humans investigating the TB vaccine H1:CAF01, Imatinib combining a new liposomal adjuvant CAF01 with a well-defined TB subunit vaccine antigen H1. In this study, the vaccine was safe, well tolerated and generated long-lasting (3 years) T-cell responses, as monitored by IFN-γ ELISpot, intracellular cytokine staining and multiplex analysis of 14 secreted cytokines and chemokines. Two vaccinations with H1:CAF01 did not lead to any serious adverse reactions. All adverse events that were assessed as related to the vaccination were mild or moderate and disappeared within days. The main

H1:CAF01-related adverse event was stiffness and pain at the injection site, of mild to moderate severity, Phospholipase D1 mostly the day after administration of the vaccine. A mild to moderate transient local reactogenicity of H1:CAF01 was anticipated based on the findings in nonclinical GLP toxicity studies and was also observed in previous vaccination studies in humans with the H1 antigen [6], [7] and [21]. The vaccine did not consistently affect hematological or biochemical measurements. In conclusion, this clinical trial found no safety concerns associated with the administration of the CAF01-adjuvanted vaccine to healthy adults. As this was a phase I trial, the limitation to this conclusion is the limited number of subjects, and we can exclude with certainty only frequently occurring adverse reactions.