Safety and immunogenicity of the H56:IC31 tuberculosis vaccine candidate in adults successfully treated for drug-susceptible pulmonary TB: a phase 1 randomized trial.

ABSTRACT

BACKGROUND: H56IC31 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 H56IC31 in individuals treated for TB. METHODS: 22 adults confirmed to be Mtb negative (by 2 GeneXpert tests or 2 sputum cultures) after four-five months of TB treatment, and not more than 28 days after completion of TB treatment, were randomized to receive two doses of H56IC31 (5 mg H56500 nmol IC31; N=16) or placebo (N=6) 56 days apart. Participants were followed for 420 days for safety and immunogenicity. RESULTS: H56IC31 vaccination was associated with an acceptable safety profile, consisting mostly of mild self-limited injection site reactions. No serious adverse events, and no vaccine-related severe adverse events, were reported. H56IC31 induced a CD4+ T-cell response for Ag85B and ESAT-6, with ESAT-6 being immunodominant, which persisted through six 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: H56IC31 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. TRIAL REGISTRATION ClinicalTrials.gov, NCT02375698.