Abstract Body


Persons with tuberculosis (TB) who are deemed cured on completion of treatment remain at higher risk of recurrent disease. The TB vaccine candidate H56:IC31 has been shown to be safe and immunogenic in phase 1/2 studies, including in treated TB patients. Whether H56:IC31 can reduce the risk of recurrent TB is unknown.


In a multicenter, double-blind, randomized, placebo-controlled, event-driven trial in South Africa and Tanzania, we enrolled participants aged 18-60 years, without HIV, who were sputum smear-negative upon completion of treatment for drug-sensitive pulmonary TB. Participants were randomly assigned (1:1) to receive two doses of H56:IC31 or placebo (56 days apart) and followed up for 1 year. The primary endpoint was recurrence of culture-confirmed pulmonary TB. Vaccine efficacy (VE) estimates with 95% confidence interval (95%CI) were derived from Cox proportional hazard models. Secondary endpoints included TB relapse or reinfection as differentiated by whole genome sequencing of paired sputum samples, safety, and immunogenicity.


831 participants (mean age 34.7 years; 27.6% female; 66.1% black African; 76% from South Africa) were enrolled; 415 received H56:IC31 and 416 placebo. In the primary analysis, recurrent TB was observed in 23 (12 relapse; 8 reinfection; 3 indeterminate) of 400 participants (5.8%) in the H56:IC31 group; and 14 (6 relapse; 7 reinfection; 1 indeterminate) of 406 participants (3.4%) in the placebo group. VE for recurrence was -73.8% (95%CI:-246.9 to 9.8%; P=0.10). VE for relapse was -116.1% (-522.2 to 16.3%; P=0.11) and for reinfection VE was -21.1% (-245.3 to 56.5%; P=0.71). Participants in the H56:IC31 group reported more mild-to-moderate local injection reactions than in the placebo group. No H56:IC31-related serious adverse events were observed. Participants receiving H56:IC31 mounted robust H56-specific CD4+ T cell responses and H56-specific humoral (serum IgG) responses.


This is the first reported trial with a prevention of recurrent TB design. Vaccination with H56:IC31 upon treatment completion for pulmonary tuberculosis did not reduce the risk of recurrent tuberculosis. H56:IC31 was well-tolerated and immunogenic, but may have increased the risk of relapse by endogenous strains.