Safety and Immunogenicity of the H56:IC31 Tuberculosis Vaccine Candidate in Adults Successfully Treated for Drug-Susceptible Pulmonary Tuberculosis: A Phase 1 Randomized Trial.

Background: H56:IC31 is a candidate vaccine against tuberculosis (TB) with the potential to reduce TB recurrence rate. It is thus important for future clinical trials to demonstrate safety and immunogenicity of H56:IC31 in individuals treated for TB.
Methods: Twenty-two adults confirmed to be Mycobacterium tuberculosis negative (by 2 GeneXpert tests or 2 sputum cultures) after 4-5 months of TB treatment, and not more than 28 days after completion of TB treatment, were randomized to receive 2 doses of H56:IC31 (5 mg H56:500 nmol IC31; n = 16) or placebo (n = 6) 56 days apart. Participants were followed for 420 days for safety and immunogenicity.
Results: H56:IC31 vaccination was associated with an acceptable safety profile, consisting mostly of mild self-limited injection site reactions. No serious adverse events or vaccine-related severe adverse events were reported. H56:IC31 induced a CD4+ T-cell response for Ag85B and ESAT-6, with ESAT-6 being immunodominant, which persisted through 6 months after the last vaccination. There was some evidence of CD8+ T-cell responses for both Ag85B and ESAT-6, but to a lesser extent than CD4+ responses.
Conclusions: H56:IC31 was associated with an acceptable safety profile, and induced a predominant CD4+ T-cell response, in adults recently treated for drug-susceptible, uncomplicated pulmonary TB.
Clinical Trials Registration: NCT02375698.
Competing Interests: Potential conflicts of interest. P. L. A., I. K., M. R., and A. H. B. were employed at SSI, the developer of H56:IC31. P. L. A. is the inventor of patents related to H56:IC31. All rights have been assigned to SSI, a Danish not-for-profit institute under the Ministry of Health. D. T. was employed by Aeras (now IAVI) during the conduct of this study and is now an independent consultant. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
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